Systems and methods for heart valve therapy

ABSTRACT

Prosthetic mitral valves described herein can be deployed using a transcatheter mitral valve delivery system and technique to interface and anchor in cooperation with the anatomical structures of a native mitral valve. This document describes prosthetic heart valve designs that interface with native mitral valve structures to create a fluid seal, thereby minimizing mitral regurgitation and paravalvular leaks. This document also describes prosthetic heart valve designs and techniques to manage blood flow through the left ventricular outflow tract. In addition, this document describes prosthetic heart valve designs and techniques that reduce the risk of interference between the prosthetic valves and chordae tendineae.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.14/673,055 filed Mar. 30, 2015, which is a continuation of U.S. patentapplication Ser. No. 14/671,577 filed Mar. 27, 2015, which claims thebenefit of U.S. Application Ser. No. 62/067,907, filed Oct. 23, 2014.The disclosure of the prior application is considered part of and isincorporated by reference in the disclosure of this application.

TECHNICAL FIELD

This document relates to prosthetic heart valves, such as prostheticmitral valves that can be implanted using transcatheter techniques.

BACKGROUND

The long-term clinical effect of valve regurgitation is recognized as asignificant contributor to cardiovascular related morbidity andmortality. Thus, for many therapies intended to treat the mitral valve,one primary goal is to significantly reduce or eliminate regurgitation.By eliminating the regurgitation at the mitral valve, the destructivevolume overload effects on the left ventricle can be attenuated. Thevolume overload of mitral regurgitation (MR) relates to the excessivekinetic energy required during isotonic contraction to generate overallstroke volume in an attempt to maintain forward stroke volume andcardiac output. It also relates to the pressure potential energydissipation of the leaking valve during the most energy-consumingportion of the cardiac cycle, isovolumetric contraction. Additionally,therapies for MR reduction can have the effect of reducing the elevatedpressures in the left atrium and pulmonary vasculature reducingpulmonary edema (congestion) and shortness of breath symptomatology.Such therapies for MR reduction may also have a positive effect on thefilling profile of the left ventricle (LV) and the restrictive LVphysiology that can result with MR. These pathophysiologic issuesindicate the potential benefits of MR therapy, but also indicate thecomplexity of the system and the need for a therapy to focus beyond theMR level or grade.

Some therapies for treating MR may worsen other (non-MR) existingpathologic conditions or create new pathologic conditions. One of theconditions to be managed is mitral stenosis or creation of an inflowgradient. That is, if a prosthetic valve system is used that does notallow for sufficient LV inflow without elevated filling pressures, thensome benefits of MR reduction may be dissipated or lost. An additionalcondition to be managed is left ventricular outflow tract (LVOT)obstruction or creation of high LVOT pressure gradients. That is, if aprosthetic valve system is used that does significantly obstructs theLVOT, then some benefits of MR reduction may be dissipated or lost.Also, if the procedure results in damage to atrial tissue at surgery, itcan increase the likelihood of the negative physiologic effect of atrialfibrillation. Further, some prosthetic valve systems may increase therisk of higher LV wall stress through an increase in LV size (LVgeometry). Due to the integral relationship of the mitral valve with LVgeometry through the papillary and chordal apparatus, LV wall stresslevels can be directly affected resulting in alterations of LV fillingand contraction mechanics. Accordingly, in some circumstances, aprosthetic valve system that worsens the geometry of the LV can counterthe benefits of MR reduction because of the alteration of contractilephysiology.

SUMMARY

This document describes prosthetic heart valves, such as prostheticmitral valves that can be implanted using transcatheter techniques. Forexample, some embodiments of a transcatheter mitral valve deliverysystem and method described herein can be deployed to interface andanchor in cooperation with the native anatomical structures of a mitralvalve. In addition, this document describes prosthetic heart valvesystems that interface with native mitral valve structures to create afluid seal, thereby minimizing MR and paravalvular leaks afterimplantation. Further, this document describes prosthetic heart valvesystems and techniques that, in particular embodiments, are configuredto manage blood flow through the left ventricular outflow tract (LVOT)and to thereby reduce the risk of full or partial blockages of the LVOT.In addition, some embodiments of the prosthetic heart valve systems andtechniques described herein may be configured to reduce the risk ofinterference between the prosthetic valves and chordae tendineae of thenative mitral valve leaflets, which can advantageously facilitate orpreserve the geometry of the LV.

Particular embodiments described herein include a mitral valvereplacement system for a heart. The system may include an expandableanchor assembly configured to implant at a native mitral valve, and theexpandable anchor assembly may include a first expandable frame that isadjustable from a delivery condition to an expanded condition. Thesystem may also include a first delivery sheath device having a distalend insertable into a left atrium and being configured to express theanchor assembly out from the distal end such that the anchor assemblyexpands within the left atrium to the expanded condition. Optionally,the system may further include a pusher instrument releasably attachableto the expandable anchor frame and being configured to longitudinallyadvance the anchor assembly within the left atrium towards an annulus ofthe native mitral valve while the anchor assembly is in the expandedcondition. Also, the system may include an artificial valve assemblycomprising a second expandable frame that is adjustable from acompressed condition to a deployed condition to selectively engage withthe anchor assembly while the anchor assembly is in the expandedcondition.

Some embodiments described herein include a method for deploying aprosthetic mitral valve system within a native mitral valve of apatient. The method may include navigating a first delivery sheathwithin the patient such that a distal end of the first delivery sheathis positioned within a left atrium. The method may also includeexpressing an anchor assembly of the prosthetic heart valve system fromthe distal end of the first delivery sheath such that the anchorassembly at least partially expands while located within the leftatrium. Further, the method may include, after expressing the anchorassembly within the left atrium, moving the anchor assembly towards anannulus of the native mitral valve.

Various embodiments described herein include a prosthetic mitral valvesystem. The system may include a valve assembly, which may include aframe member defining an outer profile and an interior frame memberspace, and an occluder disposed within the interior frame member space.The occluder may have an open configuration and a closed configuration.The frame member comprises a proximal end frame portion and a distal endframe portion. Optionally, an outer periphery of the distal end frameportion may include a generally flat region and a generally roundregion, and at least some portions of the generally flat region mayextend toward the interior frame member space.

Particular embodiments described herein include a method of using aprosthetic mitral valve system. The method may include advancing a valveassembly of the prosthetic mitral valve system toward an annulus of anative mitral valve. Optionally, the valve assembly may include a framemember defining an outer profile and an interior frame member space, andoccluder disposed within the interior frame member space. The framemember may include a proximal end frame portion and a distal end frameportion. An outer periphery of the distal end frame portion mayoptionally include a generally flat region and a generally round region,and at least some portions of the generally flat region extend towardthe interior frame member space. The method may also include anchoringthe valve assembly at the native mitral valve such that the generallyflat region is adjacent to an anterior native leaflet of the nativemitral valve.

Some embodiments described herein include a prosthetic mitral valvesystem that is implantable at a native mitral valve. The prostheticmitral valve system may include an anchor assembly defining an interioranchor assembly space and longitudinal axis. The anchor assembly mayinclude an expandable anchor frame including a hub and a sub-annularsupport arm extending from the hub. The sub-annular support arm mayextend to an anchor foot having a surface configured for engagement witha sub-annular gutter of the native mitral valve. The system may furtherinclude a valve assembly that includes an expandable valve framedefining an outer profile and an interior frame member space, and anoccluder disposed within the interior frame member space. The valveassembly may be releasably engageable with the anchor assembly withinthe interior anchor assembly space. Optionally, a distance measuredparallel to the longitudinal axis from a distal-most end of the anchorassembly to the surface is at least 14 millimeters.

Various embodiments described herein include a method of using aprosthetic mitral valve system. The method may include advancing ananchor assembly of the prosthetic mitral valve system toward an annulusof a native mitral valve. The anchor assembly may an interior anchorassembly space and longitudinal axis, and the anchor assembly mayinclude an expandable anchor frame including a hub and one or moresub-annular support arms extending from the hub. Each of the one or moresub-annular support arm may extend to an anchor foot configured toengage with a sub-annular gutter of the native mitral valve. The methodmay further include engaging the anchor assembly of the prostheticmitral valve system with tissue proximate the native mitral valve suchthat each anchor foot is engaged with the sub-annular gutter, and(optionally) such that the hub is positioned distal of the distal-mostarea of coaptation between anterior and post leaflets of the nativemitral valve.

Particular embodiments described herein include a method of sealingbetween a prosthetic mitral valve system and native leaflets of a mitralvalve. The method may include anchoring an anchor assembly of theprosthetic mitral valve system with tissue proximate to an annulus of anative mitral valve. Optionally, the anchor assembly defines an interioranchor assembly space and longitudinal axis, and the anchor assembly mayinclude an expandable anchor frame including a hub and one or moresub-annular support arms extending from the hub. Each of the one or moresub-annular support arm may extend to an anchor foot that engages with asub-annular gutter of the native mitral valve. The method may furtherinclude delivering a valve assembly of the prosthetic mitral valvesystem to engage with the anchor assembly. Optionally, the valveassembly may include: an expandable valve frame defining an outerprofile and an interior frame member space, a tissue layer disposed overat least a portion of the outer profile, and an occluder disposed withinthe interior frame member space. The tissue layer of the valve assemblycan abut with native leaflets of the mitral valve while each anchor footof the anchor assembly is engaged with the sub-annular gutter.

Some embodiments described herein include a prosthetic mitral valvesystem. The system may include an anchor assembly comprising anexpandable anchor frame and a set of sub-annular anchor feet configuredto engage with a sub-annular gutter of the native mitral valve. Thesystem may further include a valve assembly that includes: an expandablevalve frame defining an outer profile and an interior frame memberspace, a tissue layer disposed over at least a portion of the outerprofile, and an occluder mounted within the interior frame member space.Optionally, an outwardly facing periphery of the tissue layer along thevalve assembly is positioned to abut native leaflets of the mitral valvewhen the set of anchor feet of the anchor assembly is engaged with thesub-annular gutter.

Various embodiments described herein include a method for deploying aprosthetic mitral valve system within a native mitral valve of apatient. The method may comprise navigating a delivery sheath such thata distal end of the delivery sheath is positioned within a left atriumof the patient. Also, the method may include expressing, in the leftatrium, an anchor assembly of the prosthetic mitral valve system. Adistal pusher instrument may be releasably engaged with the anchorassembly. The method may further include engaging the anchor assemblywith the native mitral valve while the distal pusher instrument remainsengaged with the anchor assembly. The method may also includeexpressing, in the left atrium, a valve assembly of the prostheticmitral valve system. Optionally, the valve assembly may slidably engagedwith an exterior of the distal pusher instrument. The method may furtherinclude moving the valve assembly into an interior space defined by theanchor assembly. The moving may optionally include sliding the valveassembly along the exterior of the distal pusher catheter while thedistal pusher catheter remains engaged with to the anchor assembly. Themethod may also include, after moving the valve assembly, mounting thevalve assembly with the anchor assembly. Further, the method mayinclude, after mounting the valve assembly, decoupling the distal pusherinstrument from the anchor assembly.

Particular embodiments described herein include an implantable medicaldevice delivery system. The system may include a first deflectablecatheter defining a first lumen therethrough, and a distal end portionof the first deflectable catheter may be controllably laterallydeflectable. The system may also include a first device delivery sheathslidably disposable within the first lumen, and the first devicedelivery sheath may define a second lumen therethrough. The system mayfurther include a first device control sheath slidably disposable withinthe second lumen, and the first device control sheath may define a thirdlumen therethrough and one or more first device control wire lumens. Thesystem may also include a second deflectable catheter slidablydisposable within the third lumen, and the second deflectable cathetermay define a fourth lumen therethrough. A distal end portion of thesecond deflectable catheter may be controllably laterally deflectable.The system may further include a device pusher catheter slidablydisposable within the fourth lumen, and the device pusher catheter maydefine a fifth lumen therethrough. A distal end portion of the devicepusher catheter may be configured to releasably couple with a firstimplantable medical device.

Some embodiments described herein include a method for deploying aprosthetic mitral valve system within a native mitral valve of apatient. The method may include expanding an anchor assembly of theprosthetic heart valve system within a left atrium, while the anchorassembly is releasably secured to a first delivery catheter, such thatthe anchor assembly at least partially expands while located within theleft atrium. The method may optionally include, after expressing theanchor assembly within the left atrium, panning or rotating the anchorassembly within the left atrium by articulating a tip portion of thefirst delivery catheter.

Various embodiments described herein include a method for deploying aprosthetic mitral valve system within a native mitral valve of apatient. The method may include expressing a valve assembly of theprosthetic heart valve system within a left atrium, while the valveassembly is releasably secured to a valve delivery catheter, such thatthe valve assembly at least partially expands while located within theleft atrium. The method may optionally include, after expressing thevalve assembly within the left atrium, panning or rotating the valveassembly within the left atrium by articulating a tip portion of thevalve delivery catheter.

Some or all of the embodiments described herein may provide one or moreof the following advantages. First, some embodiments of the prostheticmitral valve systems provided herein can be used in a completelypercutaneous/transcatheter mitral replacement procedure that is safe,reliable, and repeatable by surgeons of a variety of different skilllevels. For example, in some implementations the prosthetic mitral valvesystem can establish a reliable and consistent anchor/substrate to whichthe valve/occluder structure subsequently engages. Thus, the prostheticmitral valve system can be specifically designed to make use of thegeometry/mechanics of the native mitral valve to create sufficientholding capability. In one particular aspect, the anatomical gutterfound below a native mitral valve annulus can be utilized as a site foranchoring the prosthetic mitral valve system, yet the anchoringstructure can be deployed in a matter that maintains native leafletfunction of the mitral valve, thereby providing the ability tocompletely separate and stage the implantation of the components of theprosthetic mitral valve system. Accordingly, some embodiments of theprosthetic mitral valve systems described herein are configured to beimplanted in a reliable, repeatable, and simplified procedure that isbroadly applicable to a variety of patients and physicians, while alsoemploying a significantly less invasive method.

Second, some embodiments of the prosthetic mitral valve systemsdescribed herein facilitate effective long lasting MR reduction withoutcreating negative physiologic consequences to the cardiopulmonary system(heart, lungs, peripheral vasculature) including stenosis, LV wallstress, and atrial fibrillation. Also, the system may provide a safe anddurable anchoring effect at the native mitral valve to provide aneffective mitral regurgitation therapy as well as providing structuresthat provide sealing benefits and avoid significant impairment of thechordal interface of the native mitral valve leaflets.

Third, in particular embodiments, the prosthetic mitral valve system canbe delivered to the native mitral valve using a technique in which anexpandable frame of the anchor component is at least partially expandedin the left atrium prior to reaching the mitral valve location. As such,in addition to facilitating the delivery of the anchor, the heartsurgeon or other user can visualize the expanded component (and itsorientation) within the heart before it is advanced to the annulus ofthe mitral valve (thereby permitting the user the opportunity tolaterally pivot (rotate, pan, re-orient) the expanded component prior toreaching the annulus).

Fourth, some embodiments of the prosthetic mitral valve systemsdescribed herein can be configured to partially extend into the leftventricle after implantation, yet may include a profile shape that isconfigured to reduce the likelihood of obstructing blood flow throughthe LVOT. Accordingly, even though some portions of the prostheticmitral valve systems extend into the left atrium above the mitral valveannulus (supra-annular) and other portions extend into the leftventricle below the mitral valve annulus (sub-annular), the prostheticmitral valve system is designed to account for the natural LVOT andthereby reduce the risk of full or partial blockages of the LVOT.

Fifth, in particular embodiments, the prosthetic mitral valve system caninclude two different expandable components (e.g., an anchor assemblyand a valve assembly) that are separately delivered to the implantationsite, and both components can abut and engage with native heart tissueat the mitral valve. For example, the first component (e.g., the anchorassembly) can be configured to engage with the heart tissue that is ator proximate to the annulus of the native mitral valve, and the secondcomponent (e.g., the valve assembly) can be configured to provide a sealinterface with native valve leaflets of the mitral valve.

The details of one or more embodiments of the invention are set forth inthe accompanying drawings and the description below. Other features,objects, and advantages of the invention will be apparent from thedescription and drawings, and from the claims.

DESCRIPTION OF DRAWINGS

FIG. 1 is a perspective view of a portion of a prosthetic mitral valvedeployment system in a cross-sectional view of a native human heart, inaccordance with some embodiments.

FIG. 2 shows a perspective view of a prosthetic mitral valve anchorassembly in the left atrium of the heart after the anchor assembly hasemerged from an anchor delivery sheath of the deployment system of FIG.1

FIG. 3 shows a perspective view of the anchor assembly of FIG. 2 afterbeing rotated in the left atrium so as to orient the anchor assemblygenerally perpendicular to the native mitral valve.

FIG. 4 shows a perspective view of the anchor assembly of FIG. 3 afterbeing partially advanced through the native mitral valve so as toposition projections of the anchor assembly below a sub-annular gutterof the native mitral valve.

FIG. 5 shows a perspective view of the anchor assembly in a similararrangement as shown in FIG. 4, but in a commissural cross-sectionalview of the heart (from the left side of the heart).

FIG. 6 shows a perspective view of the anchor assembly of FIG. 5 afterbeing retracted so as to position the projections of the anchor assemblyin the sub-annular gutter of the native mitral valve.

FIG. 7 shows a perspective view of the anchor assembly of FIG. 6 afterthe retraction of some members of the deployment system.

FIG. 8 is a top view of a native mitral valve and depicts a gutterperimeter of the sub-annular gutter of FIG. 7 (without the anchorassembly).

FIG. 9 shows a perspective top view of an example anchor assembly ofFIGS. 2-6 in accordance with some embodiments.

FIG. 10 shows a perspective view of the anchor assembly of FIG. 9 with acovering material disposed on portions of the anchor frame.

FIG. 11A shows a perspective top view of the anchor assembly of FIG. 9implanted within a native mitral valve (with the native mitral valveleaflets in a closed state), and FIG. 11B shows a correspondinganatomical top view of the anchor assembly of FIG. 11A.

FIG. 12A shows a perspective top view of the anchor assembly of FIG. 9implanted within the native mitral valve of FIG. 11A (with the nativemitral valve leaflets in an open state), and FIG. 12B shows acorresponding anatomical top view of the anchor assembly of FIG. 12A.

FIG. 13 shows a perspective view of the anchor assembly of FIG. 7implanted within the native mitral valve and a valve assembly deliverysheath extending into the left atrium.

FIG. 14 shows a perspective view of a valve assembly in the left atriumafter partial emergence from the valve assembly delivery sheath of FIG.13. The valve assembly is configured in a first (partially expanded)arrangement.

FIG. 15 shows a perspective view of the valve assembly of FIG. 14 withthe valve deployment system being manipulated in preparation for theinstallation of the valve assembly into the anchor assembly.

FIG. 16 shows a perspective view of the valve assembly of FIG. 15 (whilestill in the first (partially expanded) arrangement) being positionedwithin the anchor assembly.

FIG. 17 shows a perspective view of the valve assembly of FIG. 16 thevalve assembly expanded within the anchor assembly and detached from thedeployment system.

FIG. 18 shows an anterior side view of a valve frame of a valve assemblyof FIG. 17, in accordance with some embodiments.

FIG. 19 shows a bottom view of the valve frame of FIG. 18.

FIG. 20 is an exploded posterior side view of an anchor assembly andvalve assembly of FIG. 17, in accordance with some embodiments.

FIG. 21 is a top view of an example prosthetic mitral valve system thatincludes a valve assembly engaged with an anchor assembly, in accordancewith some embodiments.

FIG. 22 is a bottom view of the example prosthetic mitral valve systemof FIG. 21.

FIG. 23 shows a top view of the prosthetic mitral valve system of FIG.21 implanted within a native mitral valve. The occluder portion ofprosthetic mitral valve system is shown in a closed state.

FIG. 24 shows a top view of the prosthetic mitral valve system of FIG.21 implanted within a native mitral valve. The occluder portion of theprosthetic mitral valve system is shown in an open state.

FIG. 25 is a lateral cross-sectional top view of a heart showing themitral, aortic, tricuspid and pulmonary valves.

FIG. 26 is a schematic diagram of a cross-section of a native mitralvalve including the mitral valve annulus.

FIG. 27 is an anterior side view of a valve assembly, in accordance withsome embodiments. A sealing region of the anterior side of the valveassembly is demarcated on the valve assembly.

FIG. 28 is a posterior side view of a valve assembly, in accordance withsome embodiments. A sealing region of the posterior side of the valveassembly is demarcated on the valve assembly.

FIG. 29 is a lateral side view of a valve assembly, in accordance withsome embodiments. A sealing region of the lateral side of the valveassembly is demarcated on the valve assembly.

FIG. 30 is a schematic depiction of an anterior portion of a valveassembly in relationship to the annulus of the native mitral valve.

FIG. 31 is a schematic depiction of a commissural region portion of avalve assembly in relationship to the annulus of the native mitralvalve.

FIG. 32 is a schematic depiction of a posterior portion of a valveassembly in relationship to the annulus of the native mitral valve.

FIG. 33 is a cross-sectional view of the left side of a heart showing anexample valve assembly in relationship to the annulus of the nativemitral valve and the annulus of the aortic root.

FIG. 34 is a fluoroscopic image of a native mitral valve with an exampleprosthetic valve therein, an aortic valve, and a left ventricularoutflow track of a heart. The image also shows blood flowing from theleft ventricle to the aorta through the left ventricular outflow track.

FIG. 35 is another fluoroscopic image of a native mitral valve with anexample prosthetic valve therein, an aortic valve, and a leftventricular outflow track of a heart. The image also shows blood flowingfrom the left ventricle to the aorta through the left ventricularoutflow track.

FIG. 36 is a schematic depiction of the annulus of the native mitralvalve and the annulus of the aortic root.

FIG. 37 is a commissural cross-sectional view of a heart showing ananchor assembly of a prosthetic mitral valve engaged in the sub-annulargutter of the native mitral valve. Chordae tendineae in the leftventricle are also depicted.

FIG. 38 is a lateral cross-section of a left ventricle of a heartshowing an anchor assembly of a prosthetic mitral valve engaged in thesub-annular gutter of the native mitral valve. Chordae tendineae in theleft ventricle are also depicted.

FIG. 39 is a perspective view of an anchor assembly showing controlwires that are threaded through portions of the anchor assembly.

FIG. 40 is another perspective view of an anchor assembly showingcontrol wires that are threaded through portions of the anchor assembly.

FIG. 41 is a side view of a valve assembly frame showing control wiresthat are threaded through portions of the valve assembly frame.

FIG. 42 is a schematic diagram of a threading pattern of a proximalcontrol wire corresponding to the valve assembly frame embodiment ofFIG. 41.

FIG. 43 is a schematic diagram of a threading pattern of a mid-bodycontrol wire corresponding to the valve assembly frame embodiment ofFIG. 41.

Like reference symbols in the various drawings indicate like elements.

DETAILED DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS

This disclosure describes embodiments of a prosthetic heart valvesystem, such as prosthetic mitral valve systems, and transcathetersystems and methods for implanting prosthetic heart valve systems. Insome embodiments, the prosthetic mitral valve system can be deployed tointerface and anchor in cooperation with the native anatomicalstructures of a mitral valve (and, optionally, in a manner that permitsthe continued natural function of the chordae tendineae of the nativemitral valve leaflets even after the anchor component is deployed). Asdescribed herein, the prosthetic mitral valve system can be deployed ina manner that interfaces with native mitral valve structures to create afluid seal, thereby minimizing MR and paravalvular leaks afterimplantation. As described in more detail below, FIGS. 1-17 and 39-43describe a transcatheter mitral valve delivery system and method bywhich the prosthetic mitral valve system can be deployed to interfaceand anchor in cooperation with the anatomical structures of a nativemitral valve. Also, in FIGS. 18-32, prosthetic mitral valve features aredescribed by which the prosthetic valves interface with native mitralvalve structures to create a fluid seal, thereby reducing the likelihoodof MR and paravalvular leaks. In FIGS. 33-36, prosthetic mitral valvefeatures and techniques are described for managing blood flow throughthe left ventricular outflow tract (LVOT). In FIGS. 37-38, prostheticmitral valve features and techniques are described for reducing the riskof interference between the prosthetic valves and chordae tendineae.

Referring to FIG. 1, an example transcatheter mitral valve deliverysystem 100 can be navigated through a patient's vasculature to obtainaccess to the patient's heart 10. The transcatheter delivery system 100facilitates implantation of a prosthetic mitral valve in a beating heart10 using a percutaneous, vessel cutdown, or minimally invasive technique(without open-chest surgery). In some implementations, the transcatheterdelivery system 100 is used in conjunction with one or more imagingmodalities such as x-ray fluoroscopy, echocardiography, magneticresonance imaging, computed tomography (CT), and the like.

The heart 10 (depicted in cross-section from a posterior perspective)includes a right atrium 12, a right ventricle 14, a left atrium 16, anda left ventricle 18. A tricuspid valve 13 separates the right atrium 12from the right ventricle 14. A mitral valve 17 separates the left atrium16 from the left ventricle 18. An atrial septum 15 separates the rightatrium 12 from the left atrium 16. An inferior vena cava 11 is confluentwith the right atrium 12. It should be understood that this depiction ofthe heart 10 is somewhat stylized. The same is true for FIGS. 2-4. FIGS.1-4 provide general depictions of the approach to the mitral valve 17that is used in some implementations. But, the commissuralcross-sectional views of FIG. 5 and thereafter more accurately depictthe orientation of the prosthetic mitral valves in relation to the heart10.

In the depicted embodiment, the delivery system 100 includes a guidewire110, a primary deflectable catheter 120, and an anchor delivery sheath130. Additional components of the delivery system 100 will be describedfurther below. The anchor delivery sheath 130 is slidably (androtationally) disposed within a lumen of the primary deflectablecatheter 120. The guidewire 110 is slidably disposed within a lumen ofthe anchor delivery sheath 130. In this depiction, the anchor deliverysheath 130 has been partially extended relative to the primarydeflectable catheter 120, allowing a flared portion 132 to expandoutward, as described further below.

In the depicted implementation, the guidewire 110 is installed into theheart 10 prior to the other components of the delivery system 100. Insome embodiments, the guidewire 110 has a diameter of about 0.035 inches(about 0.89 mm). In some embodiments, the guidewire 110 has a diameterin a range of about 0.032 inches to about 0.038 inches (about 0.8 mm toabout 0.97 mm). In some embodiments, the guidewire 110 has a diametersmaller than 0.032 inches (about 0.80 mm) or larger than 0.038 inches(about 0.97 mm). In some embodiments, the guidewire 110 is made ofmaterials such as, but not limited to, nitinol, stainless steel,high-tensile-strength stainless steel, and the like, and combinationsthereof. The guidewire 110 may include various tip designs (e.g., J-tip,straight tip, etc.), tapers, coatings, covers, radiopaque (RO) markers,and other features.

In some implementations, the guidewire 110 is percutaneously insertedinto a femoral vein of the patient. The guidewire 110 is routed to theinferior vena cava 11 and into the right atrium 12. After creating anopening in the atrial septum 15 (e.g., a trans-septal puncture of thefossa ovalis), the guidewire 110 is routed into the left atrium 16.Lastly, the guidewire 110 is routed through the mitral valve 17 and intothe left ventricle 18. In some implementations, the guidewire 110 can beinstalled into the heart 10 along other anatomical pathways. Theguidewire 110 thereafter serves as a rail over which other components ofthe delivery system 100 are passed.

In the depicted implementation, the primary deflectable catheter 120 isinstalled by pushing it over the guidewire 110. In some implementations,a dilator tip is used in conjunction with the primary deflectablecatheter 120 as the primary deflectable catheter 120 is advanced overthe guidewire 110. Alternatively, a balloon catheter could be used asthe initial dilation means. After the distal end of the primarydeflectable catheter 120 reaches the left atrium 16, the dilator tip canbe withdrawn. In some embodiments, the distal end portion of the primarydeflectable catheter 120 is steerable. Using steering, the distal endportion of the primary deflectable catheter 120 can be oriented asdesired in order to navigate the patient's anatomy. For example, theprimary deflectable catheter 120 can be angled within the right atrium12 to navigate the primary deflectable catheter 120 from the inferiorvena cava 11 to the atrial septum 15.

In some embodiments, the primary deflectable catheter 120 has an outerdiameter of about 28 Fr (about 9.3 mm). In some embodiments, the primarydeflectable catheter 120 has an outer diameter in the range of about 26Fr to about 34 Fr (about 8.7 mm to about 11.3 mm). In some embodiments,the primary deflectable catheter 120 has an outer diameter in the rangeof about 20 Fr to about 28 Fr (about 6.7 mm to about 9.3 mm).

The primary deflectable catheter 120 can comprise a tubular polymeric ormetallic material. For example, in some embodiments the primarydeflectable catheter 120 can be made from polymeric materials such as,but not limited to, polytetrafluoroethylene (PTFE), fluorinated ethylenepropylene (FEP), HYTREL®, nylon, PICOFLEX®, PEBAX®, TECOFLEX®, and thelike, and combinations thereof. In alternative embodiments, the primarydeflectable catheter 120 can be made from metallic materials such as,but not limited to, nitinol, stainless steel, stainless steel alloys,titanium, titanium alloys, and the like, and combinations thereof. Insome embodiments, the primary deflectable catheter 120 can be made fromcombinations of such polymeric and metallic materials (e.g., polymerlayers with metal braid, coil reinforcement, stiffening members, and thelike, and combinations thereof).

The example delivery system 100 also includes the anchor delivery sheath130. In some implementations, after the primary deflectable catheter 120is positioned with its distal end in the left atrium 16, the anchordelivery sheath 130 is installed into a lumen of the primary deflectablecatheter 120 (over the guidewire 110) and advanced through the primarydeflectable catheter 120. As described further below, in someembodiments the anchor delivery sheath 130 is preloaded with aprosthetic valve anchor assembly and other components of the deliverysystem 100.

In some embodiments, the anchor delivery sheath 130 can be made from thematerials described above in reference to the primary deflectablecatheter 120. In some embodiments, the anchor delivery sheath 130 has anouter diameter in the range of about 20 Fr to about 28 Fr (about 6.7 mmto about 9.3 mm). In some embodiments, the anchor delivery sheath 130has an outer diameter in the range of about 14 Fr to about 24 Fr (about4.7 mm to about 8.0 mm).

In the depicted embodiment, the anchor delivery sheath 130 includes aflared distal end portion 132. In some embodiments, no such flareddistal end portion 132 is included. The flared distal end portion 132can collapse to a lower profile when constrained within the primarydeflectable catheter 120. When the flared distal end portion 132 isexpressed from the primary deflectable catheter 120, the flared distalend portion 132 can self-expand to the flared shape. In someembodiments, the material of the flared distal end portion 132 includespleats or folds, may be a continuous flared end or may be separated intosections such as flower pedals, and may include one or more resilientelements that bias the flared distal end portion 132 to assume theflared configuration in the absence of restraining forces (such as fromcontainment within the primary deflectable catheter 120). The flareddistal end portion 132 can be advantageous, for example, for recapturingthe anchor assembly within the lumen of the anchor delivery sheath 130after the anchor assembly has been expressed from the flared distal endportion 132.

In some embodiments, the maximum outer diameter of the flared distal endportion 132 is in a range of about 30 Fr to about 34 Fr (about 10.0 mmto about 11.3 mm). In some embodiments, the maximum outer diameter ofthe flared distal end portion 132 is in a range of about 32 Fr to about44 Fr (about 10.7 mm to about 14.7 mm). In some embodiments, the maximumouter diameter of the flared distal end portion 132 is in a range ofabout 24 Fr to about 30 Fr (about 8.0 mm to about 10.0 mm). In someembodiments, the maximum outer diameter of the flared distal end portion132 is less than about 24 Fr (about 8.0 mm) or greater than about 44 Fr(about 14.7 mm).

Referring to FIG. 2, additional components of the example deliverysystem 100 can include a proximal control sheath 140, a secondarydeflectable catheter 150, and a distal pusher catheter 160. The proximalcontrol sheath 140 is slidably disposed within a lumen of the anchordelivery sheath 130. The secondary deflectable catheter 150 is slidablydisposed within a lumen of the proximal control sheath 140. The distalpusher catheter 160 is slidably disposed within a lumen of the secondarydeflectable catheter 150. These components of the delivery system 100can be manipulated by a clinician operator to control the position andorientation of an anchor assembly 200. The anchor assembly 200 isslidably disposed over the guidewire 110.

In some implementations of delivery system 100, one or more of theproximal control sheath 140, the secondary deflectable catheter 150, thedistal pusher catheter 160, and the anchor assembly 200 have been loadedinto the anchor delivery sheath 130 prior to the advancement of theanchor delivery sheath 130 into the primary deflectable catheter 120 asshown in FIG. 1. That is, in some cases the proximal control sheath 140,the secondary deflectable catheter 150, the distal pusher catheter 160,and/or the anchor assembly 200 are already installed in the anchordelivery sheath 130 as the anchor delivery sheath 130 is distallyadvanced into the primary deflectable catheter 120 to attain thearrangement shown in FIG. 1. In other implementations, one or more ofthe proximal control sheath 140, the secondary deflectable catheter 150,the distal pusher catheter 160, and the anchor assembly 200 are distallyadvanced into the anchor delivery sheath 130 after the anchor deliverysheath 130 has been advanced into the primary deflectable catheter 120to attain the arrangement shown in FIG. 1.

The distal pusher catheter 160 is releasably coupled with a hub 210 ofthe anchor assembly 200. A proximal end of the anchor assembly 200 isalso releasably coupled to the proximal control sheath 140 by one ormore control wires 142. While the depicted embodiment includes onecontrol wire 142, in some embodiments two, three, four, five, or morethan five control wires are included.

Referring to FIGS. 39 and 40, the control wire 142 is shown in anexample engagement pattern with the anchor assembly 200. In the depictedembodiment, the control wire 142 is threaded through a plurality ofproximal portions of the anchor assembly 200. In the depictedembodiment, the control wire 142 is configured in a lasso arrangement.Accordingly, a tensioning of the control wire 142 will cause at leastthe proximal end of the anchor assembly 200 to contract. Conversely, aremoval of tension from the control wire 142 will allow the anchorassembly 200 to expand. In some embodiments, the control wire 142 isthreaded through eyelets that are disposed on various positions on theanchor assembly 200. In some embodiments, the control wire 142 isthreaded through attachment features that are disposed on variouspositions on the covering or frame of the anchor assembly 200. Thecontrol wire 142 can be tensioned or relaxed to arrive at a desiredextent of expansion of the proximal end of the anchor assembly 200(e.g., the atrial holding features 240 a, 240 b, 240 c, and 240 d,and/or the undulating supra-annular ring 250). Multiple control wires142 could also be used to achieve asymmetric, controlled expansion ofthe anchor assembly 300.

Referring again to FIG. 2, the position of the anchor assembly 200 canbe controlled by manipulating the positions of the distal pushercatheter 160 and/or the proximal control sheath 140. For example, in thedepicted embodiment the anchor assembly 200 can be expressed out fromthe anchor delivery sheath 130 (as shown in FIG. 2) by moving the distalpusher catheter 160 and/or the proximal control sheath 140 distally inrelation to the anchor delivery sheath 130. In some implementations, theexpression of the anchor assembly 200 is caused by proximally pullingback the anchor delivery sheath 130 while generally maintaining thepositions of the distal pusher catheter 160 and/or the proximal controlsheath 140. In some implementations, the expression of the anchorassembly 200 is caused by a combination of proximally pulling back theanchor delivery sheath 130 while distally extending the positions of thedistal pusher catheter 160 and/or the proximal control sheath 140.

As the anchor assembly 200 emerges from the confines of the anchordelivery sheath 130, the anchor assembly 200 expands from a low-profiledelivery configuration to a partially expanded configuration (as shownin FIG. 2). The extent of expansion of the anchor assembly 200 can be atleast partially controlled by the relative positioning of the proximalcontrol sheath 140 in relation to the distal pusher catheter 160. Forinstance, as the proximal control sheath 140 is moved proximally inrelation to the distal pusher catheter 160, the anchor assembly 200 isaxially elongated and radially contracted. Conversely, as the proximalcontrol sheath 140 is moved distally in relation to the distal pushercatheter 160, the anchor assembly 200 is axially shortened and radiallyexpanded. In some implementations, this control of the radial size ofthe anchor assembly 200 is used by a clinician during the process ofdeploying the anchor assembly 200 within the native mitral valve 17, asdescribed further below. As described further below, the control wire142 can also be used to control some radial expansion of the anchorassembly 300 (without changing the relative distance of the proximalcontrol sheath 140 in relation to the distal pusher catheter 160).

It should be understood that the prosthetic mitral valves providedherein are comprised of an anchor assembly 200 and a separable valveassembly (e.g., refer to FIGS. 14-20). The anchor assembly 200 isdeployed to an arrangement interfacing within the native mitral valve 17prior to deployment of the valve assembly. Said differently, afterimplanting the anchor assembly 200 within the native mitral valve 17,the valve assembly can then be deployed within the anchor assembly 200and within the native mitral valve 17 (as described further below).Therefore, it can be said that the prosthetic mitral valves providedherein are deployed using a staged implantation method. That is, theanchor assembly 200 is deployed in one stage, and the valve assembly isdeployed in a subsequent stage. In some implementations, the deploymentof the valve assembly takes place right after the deployment of theanchor assembly 200 (e.g., during the same medical procedure). In someimplementations, the deployment of the valve assembly takes place hours,days, weeks, or even months after the deployment of the anchor assembly200 (e.g., during a subsequent medical procedure).

The staged implantation method of the prosthetic mitral valves providedherein is facilitated by the fact that when the anchor assembly 200itself is implanted within the native mitral valve 17, the native mitralvalve 17 continues to function essentially as before the implantation ofthe anchor assembly 200 without a significant impact on cardiovascularphysiology. That is the case because, as described further below, theanchor assembly 200 interfaces and anchors within structural aspects ofthe native mitral valve 17 without substantially interfering with theleaflets or chordae tendineae of the native mitral valve 17.

Still referring to FIG. 2, in the depicted arrangement the distal endportion of the secondary deflectable catheter 150 is located at leastpartially internally within the anchor assembly 200. The secondarydeflectable catheter 150 can be manipulated by a clinician operator toreversibly bend the distal end portion of the secondary deflectablecatheter 150. As the secondary deflectable catheter 150 is bent by theclinician, other components of the delivery system 100 may bend alongwith the secondary deflectable catheter 150. For example, one or more ofthe distal pusher 160 and the proximal control sheath 140 may bend inresponse to the bending of the deflectable catheter 150. Because theanchor assembly 200 is coupled to the distal pusher 160 and the proximalcontrol sheath 140, the anchor assembly 200 can, in turn, be rotated bybending the secondary deflectable catheter 150.

Referring to FIG. 3, as described above, the secondary deflectablecatheter 150 can be articulated (also referred to as steered, deflected,bent, curved, etc.) to pivot laterally (pan, rotate, etc.) the anchorassembly 200 while the anchor assembly 200 is within the left atrium 16.Such rotation of the anchor assembly 200 is advantageous, for example,to orient the anchor assembly 200 in a desired relationship to thenative mitral valve 17 in preparation for implanting the anchor assembly200 within the native mitral valve 17. In some implementations, it isdesirable to orient the anchor assembly 200 so that its longitudinalaxis is generally perpendicular to the native mitral valve 17. Thelateral pivoting of the partially or fully expanded anchor assembly 200within the atrium 16 may be advantageous versus having to pivotlaterally the anchor assembly 200 while it is still constrained within adelivery sheath, as the latter assembly is a relatively large and stiffcatheter assembly.

In preparation for engaging the anchor assembly 200 with the nativemitral valve 17, the clinician operator may manipulate the radial sizeof the anchor frame 200 so that the anchor frame 200 can be passedthrough the native mitral valve 17 without damaging the native mitralvalve 17. For example, the clinician can move the proximal controlsheath 140 proximally in relation to the distal pusher catheter 160 toradially contract the anchor assembly 200. With the anchor assembly 200radially contracted, the anchor frame 200 can be safely passed throughthe native mitral valve 17 without damaging the native mitral valve 17.

Referring to FIG. 4, while the secondary deflectable catheter 150 isretained in its bent configuration as described in reference to FIG. 3,the distal pusher catheter 160 and the proximal control sheath 140 canbe simultaneously advanced. Because the distal pusher catheter 160 isreleasably coupled to the hub 210 of the anchor assembly 200, andbecause the proximal control sheath 140 is releasably coupled to theproximal end of the anchor assembly 200 via the one or more wires 142 aand 142 b, simultaneous advancement of the distal pusher catheter 160and the proximal control sheath 140 results in advancement of the anchorassembly 200. The anchor assembly 200 is advanced such that the distalend of anchor assembly 200 is within the left ventricle 18 while theproximal end of the anchor assembly 200 is within the left atrium 16.Hence, some portions of the anchor assembly 200 are on each side of thenative mitral valve 17.

In the depicted embodiment, the anchor assembly 200 includes four anchorfeet: a left anterior foot 220 a, a left posterior foot 220 b, a rightposterior foot 220 c, and a right anterior foot 220 d. In someembodiments, fewer or more anchor feet may be included (e.g., two,three, five, six, or more than six). In some embodiments, the anchorfeet 220 a, 220 b, 220 c, and 220 d are portions of the anchor assembly200 that are configured for contact with a sub-annular gutter 19 of thenative mitral valve 17, without penetrating tissue of the native mitralvalve 17. Accordingly, the anchor feet 220 a, 220 b, 220 c, and 220 dhave atraumatic surfaces that are generally comparable to feet. However,in some embodiments one or more of the anchor feet 220 a, 220 b, 220 c,and 220 d are configured to penetrate tissue and may have anchorfeatures such as barbs, coils, hooks, and the like.

In the arrangement of FIG. 4, the anchor feet 220 a, 220 b, 220 c, and220 d are positioned below the sub-annular gutter 19. In thisarrangement, the radial size of the anchor assembly 200 can be increasedto align the anchor feet 220 a, 220 b, 220 c, and 220 d with thesub-annular gutter 19. For example, the clinician can move the proximalcontrol sheath 140 distally in relation to the distal pusher catheter160 to radially expand the anchor assembly 200 to align the anchor feet220 a, 220 b, 220 c, and 220 d with the sub-annular gutter 19. Suchalignment can be performed in preparation for seating the anchor feet220 a, 220 b, 220 c, and 220 d within the sub-annular gutter 19.

Referring to FIG. 5, a commissural cross-sectional view of the heart 10provides another perspective of the anchor assembly 200 in the samearrangement in relation to the native mitral valve 17 as shown in FIG.4. This commissural cross-sectional view of the heart 10 is across-sectional view taken through the mitral valve 17 along a planethrough the left atrium 16 and left ventricle 18 that is parallel to theline that intersects the two commissures of the mitral valve 17 (asdescribed further in reference to FIG. 8 below). In the following FIGS.5-7 and 13-17, the commissural cross-sectional view of the heart 10 willbe used to describe the delivery system 100 and methods for deployingthe prosthetic mitral valves provided herein. The view in FIGS. 5-7 and13-17 is slightly tilted so that better visualization of the anchorassembly 200 is provided.

The anchor feet 220 a, 220 b, 220 c, and 220 d are positioned below thesub-annular gutter 19. In this position, the anchor feet 220 a, 220 b,220 c, and 220 d are positioned under the systolic and diastolicexcursions of the leaflets of the native mitral valve 17. In thisorientation, the anchor feet 220 a, 220 b, 220 c, and 220 d can bealigned with the sub-annular gutter 19 in preparation for seating theanchor feet 220 a, 220 b, 220 c, and 220 d within the sub-annular gutter19.

Referring to FIG. 6, the distal pusher 160 and the proximal controlsheath 140 can be simultaneously refracted in relation to the secondarydeflectable catheter 150 and the primary deflectable catheter 120. As aresult, the anchor feet 220 a, 220 b, 220 c, and 220 d become seated inthe sub-annular gutter 19. In this position, the anchor feet 220 a, 220b, 220 c, and 220 d are positioned under the systolic and diastolicexcursions of the leaflets of the native mitral valve 17, and the otherstructures of the anchor assembly 200 do not inhibit the movements ofthe leaflets. Therefore, with the anchor assembly 200 coupled to thestructures of the mitral valve 17 as described, the mitral valve 17 cancontinue to function as it did before the placement of the anchorassembly 200. In addition, the manner in which the anchor assembly 200interfaces with the native mitral valve 17 does not result indeformation of the native mitral valve 17. Therefore, the native mitralvalve 17 can continue to function as it did before the placement of theanchor assembly 200.

Referring to FIG. 7, with the anchor assembly 200 engaged within thenative mitral valve 17, components of the delivery system 100 can bewithdrawn from the anchor assembly 200. For example, the control wire142 can be detached from the proximal end of the anchor assembly 200.Thereafter, the proximal control sheath 140 can be withdrawn. Thesecondary deflectable catheter 150 can also be withdrawn. In fact, if sodesired, the proximal control sheath 140, the secondary deflectablecatheter 150, and the anchor delivery sheath 130 can be completelywithdrawn from the primary deflectable catheter 120. In contrast, insome implementations the distal pusher catheter 160 is advantageouslyleft attached to the hub 210 of the anchor assembly 200. As will bedescribed further below, in some implementations the distal pushercatheter 160 can be used as a rail on which a valve assembly is deployedinto the interior of the anchor assembly 200. However, in someimplementations the anchor assembly 200 is completely detached from thedelivery system 100, and the delivery system 100 is removed from thepatient. After a period of hours, days, weeks, or months, subsequent tothe deployment of the anchor assembly 200, a valve assembly can beinstalled into the anchor assembly 200 to complete the installation ofthe prosthetic mitral valve.

Referring to FIGS. 8 and 9, the anatomy of the native mitral valve 17includes some consistent and predictable structural features acrosspatients that can be utilized for engaging the anchor assembly 200therewith. For example, the native mitral valve 17 includes theaforementioned sub-annular gutter 19. In addition, the native mitralvalve 17 includes a D-shaped annulus 28, an anterolateral commissure 30a, a posteromedial commissure 30 b, a left fibrous trigone 134 a, and aright fibrous trigone 134 b. Further, the native mitral valve 17includes an anterior leaflet 20 and a three-part posterior leaflet 22.The posterior leaflet 22 includes a lateral scallop 24 a, a middlescallop 24 b, and a medial scallop 24 c. The free edges of the posteriorleaflet 22 and the anterior leaflet 20 meet along a coaptation line 32.

The D-shaped annulus 28 defines the structure from which the anteriorleaflet 20 and posterior leaflet 22 extend and articulate. The left andright fibrous trigones 134 a and 134 b are located near the left andright ends of the anterior leaflet 20 and generally adjacent the lateraland medial scallops 24 a and 24 c of the posterior leaflet 22. Thesub-annular gutter 19 runs along the annulus 28 between the left andright fibrous trigones 134 a and 134 b along the posterior leaflet 22.

The regions at or near the high collagen annular trigones 134 a and 134b can generally be relied upon to provide strong, stable anchoringlocations. The muscle tissue in the regions at or near the trigones 134a and 134 b also provides a good tissue ingrowth substrate for addedstability and migration resistance of the anchor assembly 200.Therefore, the regions at or near the trigones 134 a and 134 b define aleft anterior anchor zone 34 a and a right anterior anchor zone 34 brespectively. The left anterior anchor zone 34 a and the right anterioranchor zone 34 b provide advantageous target locations for placement ofthe left anterior foot 220 a and the right anterior foot 220 drespectively.

The depicted embodiment of the anchor assembly 200 also includes theleft posterior foot 220 b and the right posterior foot 220 c. Aspreviously described, the left posterior foot 220 b and the rightposterior foot 220 c can also be advantageously positioned in thesub-annular gutter 19 in order to provide balanced and atraumaticcoupling of the anchor assembly 200 to the native mitral valve 17.Therefore, a left posterior anchor zone 34 b and a right anterior anchorzone 34 c are defined in the sub-annular gutter 19. The left posterioranchor zone 34 b and the right anterior anchor zone 34 c can receive theleft posterior foot 220 b and the right posterior foot 220 crespectively. In some implementations, the locations of the leftposterior anchor zone 34 b and the right anterior anchor zone 34 c mayvary from the depicted locations while still remaining within thesub-annular gutter 19. It should be understood that the depicted anchorassembly 200 is merely one non-limiting example of the anchor assembliesprovided within the scope of this disclosure.

In some embodiments, the anchor assembly 200 includes supra-annularstructures and sub-annular structures. For example, the sub-annularstructures of the anchor assembly 200 include the aforementioned anchorfeet 220 a, 220 b, 220 c, and 220 d, and the hub 210. In someembodiments, as described above, the hub 210 functions as a connectionstructure for the delivery system 100 (e.g., refer to FIG. 2). Inaddition, the hub 210 can function as a stabilizing structural componentfrom which a left anterior sub-annular support arm 230 a, a leftposterior sub-annular support arm 230 b, a right posterior sub-annularsupport arm 230 c, and a right anterior sub-annular support arm 230 dextend to the anchor feet 220 a, 220 b, 220 c, and 220 d respectively.

In some embodiments, such as the depicted embodiment, the supra-annularstructures of the anchor assembly 200 include: a left anterior atrialholding feature 240 a, a left posterior atrial holding feature 240 b, aright posterior atrial holding feature 240 c, and a right anterioratrial holding feature 240 d; an anterior anchor arch 250 a, a leftanchor arch 250 b, a posterior anchor arch 250 c, and a right anchorarch 250 d; and connection bridges 260. The anterior anchor arch 250 a,left anchor arch 250 b, posterior anchor arch 250 c, and right anchorarch 250 d are joined with each other to form an undulatingsupra-annular ring 250 that acts as a supra-annular structural elementfor the anchor assembly 200. As will be described further below, thesupra-annular ring 250 also defines an opening to a space within theinterior of the anchor assembly 200 that is configured to receive andengage with a valve assembly. The atrial holding features 240 a, 240 b,240 c, and 240 d are configured to contact the shelf-like supra-annulartissue surface above the mitral valve annulus, and to thereby stabilizethe anchor assembly 200 in supra-annular areas that are generallyopposite of the anchor feet 220 a, 220 b, 220 c, and 220 d respectively.

In some embodiments, connection bridges 260 provide enhanced stabilityand fatigue resistance from vertically oriented forces on a companionartificial valve assembly when the valve (not shown) is closed andblocking pressurized blood during systole. The anchor assembly 200 canalso include one or more holes 226 in frame portions adjacent the feet,which are additional control points for delivery and retrieval of theassembly, or could be used to secure a positional delivery frame.

In some embodiments, such as the depicted embodiment, the supra-annularstructures and sub-annular structures of the anchor assembly 200 areinterconnected by a lateral anterior inter-annular connection 270 a, alateral posterior inter-annular connection 270 b, a medial posteriorinter-annular connection 270 c, and a medial anterior inter-annularconnection 270 d. For example, the lateral anterior inter-annularconnection 270 a connects the lateral anterior anchor foot 220 a withthe lateral anterior atrial holding feature 240 a. In addition, thelateral anterior inter-annular connection 270 a connects the lateralanterior anchor foot 220 a with the anterior anchor arch 250 a and theleft anchor arch 250 b. In the depicted embodiment, each of the otherinter-annular connections 270 b, 270 c, and 270 d interconnect portionsof the supra-annular structures and sub-annular structures in mannersanalogous to that of the lateral anterior inter-annular connection 270a. For example, the lateral anterior inter-annular connection 270 bconnects the lateral anterior anchor foot 220 b with the left anchorarch 250 b and the posterior anchor arch 250 c; the lateral anteriorinter-annular connection 270 c connects the lateral anterior anchor foot220 c with the posterior anchor arch 250 c and the right anchor arch 250d; and the lateral anterior inter-annular connection 270 d connects thelateral anterior anchor foot 220 d with the right anchor arch 250 d andthe anterior anchor arch 250 a.

In some embodiments, the elongate members of the anchor assembly 200 areformed from a single piece of precursor material (e.g., sheet or tube)that is cut, expanded, and connected to the hub 210. For example, someembodiments are fabricated from a tube that is laser-cut (or machined,chemically etched, water jet cut, etc.) and then expanded and heat-setinto its final expanded size and shape. In some embodiments, the anchorassembly 200 is created compositely from multiple elongate members(e.g., wires or cut members) that are joined together with the hub 210and each other to form the anchor assembly 200.

The elongate members of the anchor assembly 200 can be comprised ofvarious materials and combinations of materials. In some embodiments,nitinol (NiTi) is used as the material of the elongate members of theanchor assembly 200, but other materials such as stainless steel, L605steel, polymers, MP35N steel, stainless steels, titanium,colbalt/chromium alloy, polymeric materials, Pyhnox, Elgiloy, or anyother appropriate biocompatible material, and combinations thereof canbe used. The super-elastic properties of NiTi make it a particularlygood candidate material for the elongate members of the anchor assembly200 because, for example, NiTi can be heat-set into a desired shape.That is, NiTi can be heat-set so that the anchor assembly 200 tends toself-expand into a desired shape when the anchor assembly 200 isunconstrained, such as when the anchor assembly 200 is deployed out fromthe anchor delivery sheath 130. A anchor assembly 200 made of NiTi, forexample, may have a spring nature that allows the anchor assembly 200 tobe elastically collapsed or “crushed” to a low-profile deliveryconfiguration and then to reconfigure to the expanded configuration asshown in FIG. 9. The anchor assembly 200 may be generally conformable,fatigue resistant, and elastic such that the anchor assembly 200 canconform to the topography of the surrounding tissue when the anchorassembly 200 is deployed in a native mitral valve of a patient.

In some embodiments, the diameter or width/thickness of one or more ofthe elongate members forming the anchor assembly 200 may be within arange of about 0.008″ to about 0.015″ (about 0.20 mm to about 0.40 mm),or about 0.009″ to about 0.030″ (about 0.23 mm to about 0.76 mm), orabout 0.01″ to about 0.06″ (about 0.25 mm to about 1.52 mm), or about0.02″ to about 0.10″ (about 0.51 mm to about 2.54 mm), or about 0.06″ toabout 0.20″ (about 1.52 mm to about 5.08 mm). In some embodiments, theelongate members forming the anchor assembly 200 may have smaller orlarger diameters or widths/thicknesses. In some embodiments, each of theelongate members forming the anchor assembly 200 has essentially thesame diameter or width/thickness. In some embodiments, one or more ofthe elongate members forming the anchor assembly 200 has a differentdiameter or width/thickness than one or more of the other elongatemembers of the anchor assembly 200. In some embodiments, one or moreportions of one or more of the elongate members forming the anchorassembly 200 may be tapered, widened, narrowed, curved, radiused, wavy,spiraled, angled, and/or otherwise non-linear and/or not consistentalong the entire length of the elongate members of the anchor assembly200. Such features and techniques can also be incorporated with thevalve assemblies of the prosthetic mitral valves provided herein.

In some embodiments, the elongate members forming the anchor assembly200 may vary in diameter, thickness and/or width so as to facilitatevariations in the forces that are exerted by the anchor assembly 200 inspecific regions thereof, to increase or decrease the flexibility of theanchor assembly 200 in certain regions, to enhance migration resistance,and/or to control the process of compression (crushability) inpreparation for deployment and the process of expansion duringdeployment of the anchor assembly 200.

In some embodiments, one or more of the elongate members of the elongatemembers forming the anchor assembly 200 may have a circularcross-section. In some embodiments, one or more of the elongate membersforming the anchor assembly 200 may have a rectangular cross-sectionalshape, or another cross-sectional shape that is not rectangular.Examples of cross-sectional shapes that the elongate members forming theanchor assembly 200 may have include circular, C-shaped, square, ovular,rectangular, elliptical, triangular, D-shaped, trapezoidal, includingirregular cross-sectional shapes formed by a braided or strandedconstruct, and the like. In some embodiments, one or more of theelongate members forming the anchor assembly 200 may be essentially flat(i.e., such that the width to thickness ratio is about 2:1, about 3:1,about 4:1, about 5:1, or greater than about 5:1). In some examples, oneor more of the elongate members forming the anchor assembly 200 may beformed using a center-less grind technique, such that the diameter ofthe elongate members varies along the length of the elongate members.

The anchor assembly 200 may include features that are directed toenhancing one or more desirable functional performance characteristicsof the prosthetic mitral valve devices. For example, some features ofthe anchor assembly 200 may be directed to enhancing the conformabilityof the prosthetic mitral valve devices. Such features may facilitateimproved performance of the prosthetic mitral valve devices by allowingthe devices to conform to irregular tissue topographies and/ordynamically variable tissue topographies, for example. Suchconformability characteristics can be advantageous for providingeffective and durable performance of the prosthetic mitral valvedevices. In some embodiments of the anchor assembly 200, some portionsof the anchor assembly 200 are designed to be more conformable thanother portions of the same anchor assembly 200. That is, theconformability of a single anchor assembly 200 can be designed to bedifferent at various areas of the anchor assembly 200.

In some embodiments, the anchor assembly 200 includes features forenhanced in vivo radiographic visibility. In some embodiments, portionsof the anchor assembly 200, such as one or more of the anchor feet 220a, 220 b, 220 c, and 220 d, may have one or more radiopaque markersattached thereto. In some embodiments, some or all portions of theanchor assembly 200 are coated (e.g., sputter coated) with a radiopaquecoating.

Still referring to FIGS. 8 and 9, as described above the anchor feet 220a, 220 b, 220 c, and 220 d are sized and shaped to engage thesub-annular gutter 19 of the mitral valve 17. In some embodiments, theanterior feet 220 a and 220 d are spaced apart from each other by adistance in a range of about 30 mm to about 45 mm, or about 20 mm toabout 35 mm, or about 40 mm to about 55 mm. In some embodiments, theposterior feet 220 b and 220 c are spaced apart from each other by adistance in a range of about 20 mm to about 30 mm, or about 10 mm toabout 25 mm, or about 25 mm to about 40 mm.

In some embodiments, the anchor feet 220 a, 220 b, 220 c, and 220 d havea height ranging from about 8 mm to about 12 mm, or more than about 12mm. In some embodiments, the anchor feet 220 a, 220 b, 220 c, and 220 dhave a gutter engaging surface area (when fabric covered) ranging fromabout 6 mm² to about 24 mm². In some embodiments, the anchor feet 220 a,220 b, 220 c, and 220 d each have essentially the same gutter engagingsurface area. In particular embodiments, one or more of the anchor feet220 a, 220 b, 220 c, and 220 d has a different gutter engaging surfacearea than one or more of the other anchor feet 220 a, 220 b, 220 c, and220 d. The anchor feet 220 a, 220 b, 220 c, and 220 d can have widthsranging within about 1.5 mm to about 4.0 mm or more, and lengths rangingwithin about 3 mm to about 6 mm or more. The anchor feet 220 a, 220 b,220 c, and 220 d are sized and shaped so that the anchor assembly 200does not significantly impair the natural function of mitral valvechordae tendineae, the native mitral valve leaflets, and papillarymuscles even after the anchor assembly is anchored at the mitral valvesite.

As described previously, the anchor assembly 200 is designed to avoidinterference with the functioning of the native mitral valve 17.Therefore, the anchor assembly 200 can be implanted within the nativemitral valve 17 some time prior to the deployment therein of areplacement valve assembly, without degradation of valve 17 functionduring the period of time between the anchor implantation and the valveimplantation (whether that time is on the order of minutes, or evenseveral days or months). To avoid such interference between the anchorassembly 200 and the native mitral valve 17, the inter-annularconnections 270 a, 270 b, 270 c, and 270 d pass through the coaptationline 32 approximately. More particularly, the left anteriorinter-annular connection 270 a passes through the coaptation line 32adjacent to the anterolateral commissure 30 a. In like manner, the rightanterior inter-annular connection 270 d passes through the coaptationline 32 adjacent to the posteromedial commissure 30 b. In someimplementations, the left posterior inter-annular connection 270 b andright posterior inter-annular connection 270 c pass through the nativemitral valve 17 in locations that are posteriorly biased from thenatural coaptation line 32. The posterior leaflet 22 will tend tocompliantly wrap around the left posterior inter-annular connection 270b and right posterior inter-annular connection 270 c to facilitatesealing of the mitral valve 17, with the anchor assembly 200 coupledthereto.

In reference to FIG. 10, in some embodiments the anchor assembly 200includes a covering material 270 disposed on one or more portions of theanchor assembly 200. The covering material 270 can provide variousbenefits. For example, in some implementations the covering material 270can facilitate tissue ingrowth and/or endothelialization, therebyenhancing the migration resistance of the anchor assembly 200 andpreventing thrombus formation on blood contact elements. In anotherexample, as described further below, the covering material 270 can beused to facilitate coupling between the anchor assembly 200 and a valveassembly that is received therein. The cover material 270 also preventsor minimizes abrasion and/or fretting between the anchor assembly 200and valve assembly 300. The cover material 270 also prevents valve outertissue abrasion related wear.

In the depicted embodiment, the covering material 270 is disposedessentially on the entire anchor assembly 200. In some embodiments, thecovering material 270 is disposed on one or more portions of the anchorassembly 200, while one or more other portions of the anchor assembly200 do not have the covering material 270 disposed thereon. While thedepicted embodiment includes the covering material 270, the coveringmaterial 270 is not required in all embodiments. In some embodiments,two or more portions of covering material 270, which can be separatedand/or distinct from each other, can be disposed on the anchor assembly200. That is, in some embodiments a particular type of covering material270 is disposed on some areas of the anchor assembly 200 and a differenttype of covering material 270 is disposed on other areas of the anchorassembly 200.

In some embodiments, the covering material 270, or portions thereof,comprises a fluoropolymer, such as an expanded polytetrafluoroethylene(ePTFE) polymer. In some embodiments, the covering material 270, orportions thereof, comprises a polyester, a silicone, a urethane,ELAST-EON™ (a silicone and urethane polymer), another biocompatiblepolymer, DACRON®, polyethylene terephthalate (PET), copolymers, orcombinations and subcombinations thereof. In some embodiments, thecovering material 270 is manufactured using techniques such as, but notlimited to, extrusion, expansion, heat-treating, sintering, knitting,braiding, weaving, chemically treating, and the like. In someembodiments, the covering material 270, or portions thereof, comprises abiological tissue. For example, in some embodiments the coveringmaterial 270 can include natural tissues such as, but not limited to,bovine, porcine, ovine, or equine pericardium. In some such embodiments,the tissues are chemically treated using glutaraldehyde, formaldehyde,or triglycidylamine (TGA) solutions, or other suitable tissuecrosslinking agents.

In the depicted embodiment, the covering material 270 is disposed on theinterior and the exterior of the anchor assembly 200. In someembodiments, the covering material 270 is disposed on the just theexterior of the anchor assembly 200. In some embodiments, the coveringmaterial 270 is disposed on the just the interior of the anchor assembly200. In some embodiments, some portions of the anchor assembly 200 arecovered by the covering material 270 in a different manner than otherportions of the anchor assembly 200.

In some embodiments, the covering material 270 is attached to at leastsome portions of the anchor assembly 200 using an adhesive. In someembodiments, FEP (fluorinated ethylene propylene) is used as an adhesiveto attach the covering material 270 to the anchor assembly 200, orportions thereof. For example, an FEP coating can be applied to some orall portions of the anchor assembly 200, and the FEP can act as abonding agent to adhere the covering material 270 to the anchor assembly200. In some embodiments, wrapping, stitching, lashing, banding, and/orclips, and the like can be used to attach the covering material 270 tothe anchor assembly 200. In some embodiments, a combination oftechniques are used to attach the covering material 270 to the anchorassembly 200.

In some embodiments, the covering material 270, or portions thereof, hasa microporous structure that provides a tissue ingrowth scaffold fordurable sealing and/or supplemental anchoring strength of the anchorassembly 200. In some embodiments, the covering material 270 is made ofa membranous material that inhibits or reduces the passage of bloodthrough the covering material 270. In some embodiments, the coveringmaterial 270, or portions thereof, has a material composition and/orconfiguration that inhibits or prevents tissue ingrowth and/orendothelialization to the covering material 270.

In some embodiments, the covering material 270 can be modified by one ormore chemical or physical processes that enhance certain physicalproperties of the covering material 270. For example, a hydrophiliccoating may be applied to the covering material 270 to improve thewettability and echo translucency of the covering material 270. In someembodiments, the covering material 270 may be modified with chemicalmoieties that promote or inhibit one or more of endothelial cellattachment, endothelial cell migration, endothelial cell proliferation,and resistance to thrombosis. In some embodiments, the covering material270 may be modified with covalently attached heparin or impregnated withone or more drug substances that are released in situ.

In some embodiments, covering material 270 is pre-perforated to modulatefluid flow through the covering material 270 and/or to affect thepropensity for tissue ingrowth to the covering material 270. In someembodiments, the covering material 270 is treated to make the coveringmaterial 270 stiffer or to add surface texture. For example, in someembodiments the covering material 270 is treated with FEP powder toprovide a stiffened covering material 270 or roughened surface on thecovering material 270. In some embodiments, selected portions of thecovering material 270 are so treated, while other portions of thecovering material 270 are not so treated. Other covering material 270material treatment techniques can also be employed to provide beneficialmechanical properties and tissue response interactions. In someembodiments, portions of the covering material 270 have one or moreradiopaque markers attached thereto to enhance in vivo radiographicvisualization.

Referring now to FIGS. 11A and 12A, the anchor assembly 200 is shownimplanted within a native mitral valve 17. FIGS. 11B and 12B arephotographs that correspond to FIGS. 11A and 12A respectively. In FIG.11A, the mitral valve 17 is shown in a closed state. In FIG. 12A, themitral valve 17 is shown in an open state. These illustrations are fromthe perspective of the left atrium looking towards the mitral valve 17.For instance, in FIG. 12A chordae tendineae 40 are visible through theopen leaflets of the mitral valve 17.

These figures illustrate the supra-annular structures and sub-annularstructures of the anchor assembly 200 in their relationships with thenative mitral valve 17. For example, the closed state of the nativemitral valve 17 in FIG. 11A allows visibility of the supra-annularstructures such as the left anterior atrial holding feature 240 a, theleft posterior atrial holding feature 240 b, the right posterior atrialholding feature 240 c, and the right anterior atrial holding feature 240d. In addition, the anterior anchor arch 250 a, the left anchor arch 250b, the posterior anchor arch 250 c, the right anchor arch 250 d, and theconnection bridges 260 are visible. However, the sub-annular structuresare not visible in FIG. 11A because such structures are obstructed fromview by the anterior leaflet 20 and the three-part posterior leaflet 24a, 24 b, and 24 c.

In contrast, in FIG. 12A certain sub-annular structures of the anchorassembly 200 are visible because the native mitral valve 17 is open. Forexample, sub-annular support arms 230 a, 230 b, 230 c, and 230 d and hub210 are in view through the open mitral valve 17. Nevertheless, theanchor feet 220 a, 220 b, 220 c, and 220 d remain out of view because oftheir location within the sub-annular gutter of the mitral valve 17.

Referring to FIG. 13, after implantation of the anchor assembly 200within the native mitral valve 17 (as performed, for example, inaccordance with FIGS. 1-7 described above), a valve delivery sheath 170of the delivery system 100 can be used to deploy a valve assembly withinthe anchor assembly 200. As described above in reference to FIG. 7, withthe distal pusher catheter 160 coupled with the hub 210 of the anchorassembly 200, the distal pusher catheter 160 can be used to guide thevalve assembly into the interior of the anchor assembly 200.

In some implementations, with the primary deflectable catheter 120positioned with its distal end in the left atrium 16, the valve deliverysheath 170 is installed into a lumen of the primary deflectable catheter120 (over the distal pusher catheter 160) and advanced through theprimary deflectable catheter 120. As described further below, in someembodiments the valve delivery sheath 170 is preloaded with a prostheticvalve assembly and other components of the delivery system 100. Theprimary deflectable catheter 120 may be the same catheter that was usedto deliver the anchor assembly 200, or it may be a different catheter(but still referred to here as the primary deflectable catheter 120 forsimplicity sake).

In some embodiments, the valve delivery sheath 170 can be made from thematerials described above in reference to the primary deflectablecatheter 120. In some embodiments, the valve delivery sheath 170 has anouter diameter in the range of about 20 Fr to about 28 Fr (about 6.7 mmto about 9.3 mm). In some embodiments, the valve delivery sheath 170 hasan outer diameter in the range of about 14 Fr to about 24 Fr (about 4.7mm to about 8.0 mm).

In the depicted embodiment, the valve delivery sheath 170 includes aflared distal end portion 172. In some embodiments, no such flareddistal end portion 172 is included. The flared distal end portion 172can collapse to a lower profile when constrained within the primarydeflectable catheter 120. When the flared distal end portion 172 isexpressed from the primary deflectable catheter 120, the flared distalend portion 172 can self-expand to the flared shape. In someembodiments, the material of the flared distal end portion 172 includespleats or folds, may be a continuous flared end or may be separated intosections such as flower pedals, and may include one or more resilientelements that bias the flared distal end portion 172 to assume theflared configuration in the absence of restraining forces (such as fromcontainment within the primary deflectable catheter 120). The flareddistal end portion 172 can be advantageous, for example, for recapturingthe valve assembly within the lumen of the valve delivery sheath 170after the valve assembly has been expressed from the flared distal endportion 172.

In some embodiments, the maximum outer diameter of the flared distal endportion 172 is in a range of about 30 Fr to about 34 Fr (about 10.0 mmto about 11.3 mm). In some embodiments, the maximum outer diameter ofthe flared distal end portion 172 is in a range of about 32 Fr to about44 Fr (about 10.7 mm to about 14.7 mm). In some embodiments, the maximumouter diameter of the flared distal end portion 172 is in a range ofabout 24 Fr to about 30 Fr (about 8.0 mm to about 10.0 mm). In someembodiments, the maximum outer diameter of the flared distal end portion172 is less than about 24 Fr (about 8.0 mm) or greater than about 44 Fr(about 14.7 mm).

Referring to FIG. 14, in some implementations the valve delivery sheath170 can be withdrawn into the primary deflectable catheter 120 while avalve delivery catheter 180 is held substantially stationary to expressa valve assembly 300 from a lumen of the valve delivery sheath 170. Thevalve delivery sheath 170 and the valve delivery catheter 180 areadditional components in some embodiments of the example delivery system100.

The valve assembly 300 can be releasably coupled to the valve deliverycatheter 180 and retained in a low-profile configuration. In someembodiments, both the distal and proximal ends of the valve assembly 300are releasably coupled to the valve delivery catheter 180. In someembodiments, just one of the distal end or the proximal end of the valveassembly 300 is releasably coupled to the valve delivery catheter 180.In particular embodiments, one or more control wires may be included toreleasably couple one or more portions of the valve assembly 300 to thevalve delivery catheter 180.

Referring to FIGS. 41-43, the valve assembly 300 is releasably coupledto the valve delivery catheter 180 via a proximal control wire 342 a anda mid-body control wire 342 b. The control wires 342 a and 342 b arethreaded through one or more lumens within the valve delivery catheter180. The control wires 342 a and 342 b exit the valve delivery catheter180 and pass through eyelets on the proximal end and mid-body portionsof the valve assembly 300 respectively. The control wires 342 a and 342b are then threaded back into the valve delivery catheter 180. Bymanipulating the control wires 342 a and 342 b, a clinician operator cancontrol the valve assembly 300. For example, the expansion andcontraction of the valve assembly 300 can be controlled, and thedetachment of the valve assembly 300 from the valve delivery cathetercan be controlled, by manipulating the tension and position of thecontrol wires 342 a and 342 b within the delivery catheter 180.

Referring again to FIG. 14, a lumen of the valve delivery catheter 180can slidably surround the distal pusher catheter 160. Therefore,advancement of the valve delivery catheter 180 results in advancement ofthe valve assembly 300 over the distal pusher catheter 160 towards theanchor assembly 200.

Referring to FIGS. 15 and 16, the delivery system 100 can be manipulatedby a clinician operator to perform a lateral pivot (panning, rotation,etc.) of the valve assembly 300 within the left atrium 16. The rotationof the valve assembly 300 changes the alignment of the valve assembly300 from being generally axial with the distal end portion of theprimary deflectable catheter 120 to being generally axial with theanchor assembly 200 (in preparation for installation of the valveassembly 300 into the interior of the anchor assembly 200).

In some implementations, the aforementioned rotation of the valveassembly 300 can be performed as follows. As shown in FIG. 15, becauseof the influence from the primary deflectable catheter 120 on the valvedelivery catheter 180, the axis of the valve assembly 300 is initiallyin general alignment with the axis of the distal end portion of theprimary deflectable catheter 120. From this arrangement, a simultaneouscounter movement between the distal pusher catheter 160 and the valvedelivery catheter 180 can be performed by the clinician to rotate thevalve assembly 300. That is, as the distal pusher catheter 160 is pulledproximally, the valve delivery catheter 180 is pushed distally. As aresult of that counter movement, the valve assembly 300 rotates in arelatively tight radius, as required by the confines of the left atrium16. Thereafter, the valve delivery catheter 180 can be advanced furtherso that the valve assembly 300 is coaxially positioned within theinterior of the anchor assembly 200 as shown in FIG. 16.

Referring now also to FIG. 17, in some embodiments the valve assembly300 and the anchor assembly 200 become aligned with each othercoaxially, linearly (along their axes), and rotationally prior to orduring the expansion of the valve assembly 300, resulting in engagementbetween the valve assembly 300 and the anchor assembly 200. Thereafter,the delivery system 100 can be withdrawn from the heart 10 and theprosthetic mitral valve can perform its function.

Coaxial alignment between the valve assembly 300 and the anchor assembly200, as described above, is achieved by virtue of the valve deliverycatheter 180 being slidably disposed over the distal pusher catheter160. Linear alignment between the valve assembly 300 and the anchorassembly 200 can be achieved by the interaction of a distal end feature182 of the valve delivery catheter 180 and the hub 210 of the anchorassembly 200. For example, in some embodiments an abutting of the distalend feature 182 and the hub 210 can result in proper linear alignmentbetween the valve assembly 300 and the anchor assembly 200.

Relative rotational alignment between the valve assembly 300 and theanchor assembly 200 (about their axes) can be achieved in variousmanners. For example, in some embodiments the valve delivery catheter180 is mechanically keyed to the distal pusher catheter 160 to slidablyfix a desired rotational alignment between the valve assembly 300 andthe anchor assembly 200. In some embodiments, other types of mechanicalfeatures (e.g., pins/holes, protrusions/receptacles, etc.) can beincluded to facilitate a desired rotational/spin alignment between thevalve assembly 300 and the anchor assembly 200. Alternatively, oradditionally, radiopaque markers can be included on the valve assembly300 and on the anchor assembly 200 in locations and/or patterns that areindicative of the relative rotational orientation (about their axes) ofthe valve assembly 300 and the anchor assembly 200. In some embodiments,(e.g., when the valve delivery catheter 180 “torqueable”) the valvedelivery catheter 180 can be rotated about its axis until the markersare in proper position relative to the anchor assembly 200, prior tofinal expansion of valve assembly 300. Fluoroscopy can be used to attaina desired relative orientation of the radiopaque markers, and of thevalve assembly 300 and the anchor assembly 200 correspondingly.

Referring to FIGS. 18 and 19, an example valve assembly 300 is shownwithout any covering or valve/occluder leaflets. Hence, a valve assemblyframe 301 of the valve assembly 300 is shown. FIG. 18 shows an anteriorside view of the valve assembly frame 301, and FIG. 19 shows a bottomview of the valve assembly frame 301. The valve assembly 300 can beconstructed using any of the various materials and manufacturingtechniques described above in reference to the anchor frame 200 (e.g.,refer to FIG. 9). It should be understood that the depicted valveassembly 300 is merely one non-limiting example of the valve assembliesprovided within the scope of this disclosure.

The valve assembly 300 includes a proximal end portion 302 and a distalend portion 304. The valve assembly includes a flared external skirtportion 303 and defines an interior orifice portion 305. When the valveassembly 300 is implanted in a native mitral valve, the proximal endportion 302 is located supra-annular (in the left atrium) and the distalend portion 304 is located sub-annular (in the left ventricle). Theproximal end portion 302 defines the generally circular entrance orificeof the valve assembly 300, as described further below.

In the depicted embodiment, the valve assembly 300 generally flaresoutward along a distal direction. Said differently, the distal endportion 304 is flared outward in comparison to the proximal end portion302. Accordingly, the proximal end portion 302 defines a smaller outerprofile in comparison to the distal end portion 304. However, someregions of the distal end portion 304 bow inwardly. In particular, forexample, a posteromedial commissural corner 330 a and anterolateralcommissural corner 330 b of the valve assembly 300 may bow inwardly. Itshould be understood that the outward flare of the distal end portion304 in comparison to the proximal end portion 302 is merely one exampleconfiguration for a profile of the valve assembly 300. In someembodiments, for example, a shoulder (a portion of the valve assembly300 having the largest outer periphery) is located proximal of themiddle of the valve assembly 300.

The valve assembly 300 also includes an anterior side 306 between theposteromedial commissural corner 330 a and anterolateral commissuralcorner 330 b. When the valve assembly 300 is implanted in a nativemitral valve, the anterior side 306 faces the anterior leaflet of thenative mitral valve. The anterior side 306 of the distal end portion 304defines a generally flat surface, whereas the other sides of the distalend portion 304 are rounded. Hence, the periphery of the distal endportion 304 is generally D-shaped. The D-shaped periphery of the distalend portion 304 provides the valve assembly 300 with an advantageousouter profile for interfacing and sealing with the native mitral valve.As described further below, sealing is attained by coaptation betweenthe D-shaped periphery of the distal end portion 304 and the leaflets ofthe native mitral valve, and, in some embodiments, between the D-shapedperiphery in the region of the skirt 303 with the native valve annulus.

In the depicted embodiment, the proximal end portion 302 of the valveassembly 300 includes three atrial leaflet arches 310 a, 310 b, and 310c that together define an undulating ring at the proximal end portion302. Each of the leaflet arches 310 a, 310 b, and 310 c includes an apexhaving an attachment hole 312 a, 312 b, and 312 c respectively. In someembodiments, the attachment holes 312 a, 312 b, and 312 c are used forcoupling the proximal end of the valve assembly 300 to a deliverycatheter (e.g., valve delivery catheter 180 of FIGS. 14-16).

The valve assembly 300 also includes three commissural posts 320 a, 320b, and 320 c that each extend distally from the intersections of thethree leaflet arches 310 a, 310 b, and 310 c. The commissural posts 320a, 320 b, and 320 c are disposed at about 120° apart from each other.The commissural posts 320 a, 320 b, and 320 c each have a series ofholes that can be used for attachment of leaflets, such as by suturing.The three leaflet arches 310 a, 310 b, and 310 c and the threecommissural posts 320 a, 320 b, and 320 c are areas on the valveassembly 300 to which three prosthetic valve leaflets become attached tocomprise a tri-leaflet occluder (e.g., refer to FIGS. 22-25).

As best seen in FIG. 19, the three leaflet arches 310 a, 310 b, and 310c and the commissural posts 320 a, 320 b, and 320 c define a generallycylindrical frame for the tri-leaflet occluder construct. As such, thevalve assembly 300 provides a proven and advantageous frameconfiguration for the tri-leaflet occluder. The tri-leaflet occluderprovides open flow during diastole and occlusion of flow during systole.

Referring to FIG. 20, an exploded depiction of an example prostheticmitral valve 400 includes an anchor assembly 200 and a valve assembly300. This figures provides a posterior side view of the anchor assembly200 and the valve assembly 300.

The valve assembly 300 includes a covering 340. The covering 340 can bemade of any of the materials and constructed using any of the techniquesdescribed above in reference to covering 270. Additionally, in someembodiments the covering 340 can comprise natural tissues such as, butnot limited to, bovine, porcine, ovine, or equine pericardium. In somesuch embodiments, the tissues are chemically cross-linked usingglutaraldehyde, formaldehyde, or triglycidyl amine solution, or othersuitable crosslinking agents.

When the valve assembly 300 and the anchor assembly 200 are coupledtogether, the valve assembly 300 is geometrically interlocked within theinterior of the anchor assembly 200 (e.g., in some embodiments by virtueof the tapered shape of the valve assembly 300 within the supra-annularring and interior space of the anchor assembly 200). In particular, insome embodiments the valve assembly 300 is contained within the interiorspace between the supra-annular ring 250 and the sub-annular supportarms 230 a, 230 b, 230 c, and 230 d. As described above, the interlockedarrangement between the valve assembly 300 and the anchor assembly 200is accomplished by positioning a valve assembly 300 in a low-profileconfiguration within the interior of the anchor assembly 200 and thenallowing expansion of the valve assembly 300 within the interior of theanchor assembly 200 (e.g., refer to FIGS. 16 and 17).

Referring to FIGS. 21 and 22, a deployed configuration of the exampleprosthetic mitral valve 400 includes the valve assembly 300 engagedwithin the anchor assembly 200. FIG. 21 shows a top (atrial) view of theprosthetic mitral valve 400, and FIG. 22 shows a bottom (ventricle) viewof the prosthetic mitral valve 400.

In some embodiments, such as the depicted embodiment, valve assembly 300includes three leaflets 350 a, 350 b, and 350 c that perform theoccluding function of the prosthetic mitral valve 400. The cusps of thethree leaflets 350 a, 350 b, and 350 c are fixed to the three atrialleaflet arches 310 a, 310 b, and 310 c, and to the three commissuralposts 320 a, 320 b, and 320 c (refer to FIGS. 18 and 19). The free edgesof the three leaflets 350 a, 350 b, and 350 c can seal by coaptationwith each other during systole and open during diastole.

The three leaflets 350 a, 350 b, and 350 c can be comprised of naturalor synthetic materials. For example, the three leaflets 350 a, 350 b,and 350 c can be comprised of any of the materials described above inreference to the covering 340, including the natural tissues such as,but not limited to, bovine, porcine, ovine, or equine pericardium. Insome such embodiments, the tissues are chemically cross-linked usingglutaraldehyde, formaldehyde, or triglycidyl amine solution, or othersuitable crosslinking agents. In some embodiments, the leaflets 350 a,350 b, and 350 c have a thickness in a range of about 0.005″ to about0.020″ (about 0.13 mm to about 0.51 mm), or about 0.008″ to about 0.012″(about 0.20 mm to about 0.31 mm). In some embodiments, the leaflets 350a, 350 b, and 350 c have a thickness that is less than about 0.005″(about 0.13 mm) or greater than about 0.020″ (about 0.51 mm).

In some embodiments, the occluding function of the prosthetic mitralvalve 400 can be performed using configurations other than a tri-leafletoccluder. For example, bi-leaflet, quad-leaflet, or mechanical valveconstructs can be used in some embodiments.

Referring to FIGS. 23 and 24, the prosthetic mitral valve 400 is shownimplanted within a native mitral valve 17. In FIG. 23, the prostheticmitral valve 400 is shown in a closed state (occluded). In FIG. 24, theprosthetic mitral valve 400 is shown in an open state. Theseillustrations are from the perspective of the left atrium lookingtowards the mitral valve 17. For instance, in FIG. 24 the hub 210 andthe sub-annular support arms 230 a, 230 b, 230 c, and 230 d of theanchor assembly 200 is visible through the open leaflets 350 a, 350 b,and 350 c of the prosthetic mitral valve 400, whereas in FIG. 23 the hub210 and the sub-annular support arms 230 a, 230 b, 230 c, and 230 d arenot visible because the closed leaflets 350 a, 350 b, and 350 c blockthe hub 210 from view.

FIGS. 25-33 describe additional aspects pertaining to sealing betweennative mitral valve structures and the implantable prosthetic mitralvalves described herein. During systole, ventricle-to-atrium sealing isrelevant in order to effectively treat MR via implantation of aprosthetic mitral valve. In addition, during diastole,atrium-to-ventricle sealing between native mitral valve structures andthe prosthetic mitral valves described herein is relevant for preventingor reducing paravalvular leakage, and for good healing and chronicstability. The prosthetic mitral valves described herein are designed tohave various features that provide for effective sealing with the nativemitral valve structures.

One feature that enhances the sealing of the prosthetic mitral valvesprovided herein pertains to the shape of the prosthetic valve frameworkin relation to the shape of the native mitral valve. As described above,the annulus of a native mitral valve is generally D-shaped (e.g., referto FIG. 8). In addition, as described above, the distal end portions ofthe prosthetic mitral valves described herein are D-shaped (e.g., referto FIG. 19). In other words, the portion of the prosthetic valve that isdesigned to interface with the native valve annulus has a D-shapedprofile that is similar to the shape of the annulus. This similarity ofshapes can provide particular sealing efficacy in the areas of thelateral scallop 24 a and the medial scallop 24 c of the posteriorleaflets 22 (refer to FIG. 8).

Another feature that enhances the sealing of the prosthetic mitralvalves provided herein pertains to the size of the selected prostheticvalve in relation to the size of the native mitral valve, especiallyduring systole. In some implementations, a selected prosthetic valvewill intentionally have an outer profile (when unconstrained) that isequal to or slightly larger than the size of the annulus of the nativemitral valve. That is, in the area on the valve surface that is intendedto be adjacent to the native valve annulus, the size of the valve mayresult in a line-to-line fit or a slight interference fit with thenative valve annulus. Hence, in some implementations theatrium-to-ventricle sealing during diastole is provided by theline-to-line fit or slight interference fit between the valve and thenative valve annulus.

Another feature that enhances the sealing of the prosthetic mitralvalves provided herein pertains to the relative geometric orientation ofsealing surfaces on the prosthetic valve in relation to the annulus ofthe native mitral valve. While in some implementations, some sealing isprovided by the mechanical fit between the outer profile of the valveand the receiving structure of the native mitral valve, in someimplementations substantial sealing is provided by coaptation betweenthe native leaflets and sealing surfaces on the perimeter of theprosthetic valve (to thereby create a contact seal during diastole and aleft ventricle pressurized seal during systole). This type of sealingmay be referred to herein as a leaflet to valve body seal. As describedfurther below, the prosthetic mitral valves provided herein have sealingsurfaces that are geometrically oriented in relation to the native valveannulus so that a leaflet to valve body seal is provided. While theleaflet to valve body seal is not entirely a mechanically compressivetype of seal or an attachment onto the native tissue (active fixation)type of seal, in some embodiments such mechanical or attachment type ofseals may alternatively or additionally be incorporated.

In some implementations, an effective leaflet to valve body seal (notbased entirely on compression or attachment) may necessitate some nativeleaflet movement to the sealing surface of the valve body. Hence, avalve body shape that mimics the shape of the native mitral valve isadvantageous. As described above, in some embodiments the outerperiphery of the valve assemblies provided herein have a D-shapedperiphery that generally correlates with the D-shaped annulus of nativemitral valves. Accordingly, the movement distance of the native valveleaflets to the sealing surface of the valve body can be minimized (oressentially eliminated in some implementations), and sealing can therebybe enhanced.

In addition, an effective leaflet to valve body seal exhibits contiguouscoaptation between the native leaflets and prosthetic valve body aroundthe entire periphery of the prosthetic valve body. As described furtherbelow, the profiles of the prosthetic mitral valves provided herein aredesigned to interface with the native leaflets so as to providecontiguous coaptation around the entire periphery of the prostheticvalve. To accomplish this, in some embodiments the profile of someregions of the prosthetic mitral valves are different than the profileof other regions of the same valve (e.g., in correspondence withdiffering anatomical features in various portions of the native mitralvalve).

Referring to FIG. 25, a lateral cross-sectional atrial view of a heart10 shows the mitral valve 17, aortic valve 510, tricuspid valve, 520 andpulmonary valve 530. As described above in reference to FIG. 8, themitral valve 17 includes the anterior leaflet 20, the posterior leaflet22 (including the medial scallop 24 a, the middle scallop 24 b, and thelateral scallop 24 c), the left fibrous trigone 134 a, and the rightfibrous trigone 134 b.

In regard to sealing between a prosthetic mitral valve and a nativemitral valve, the differing anatomical features of various portions ofthe native mitral valve 17 make it advantageous to consider the mitralvalve 17 as having three distinct sealing regions that together comprisethe entirety of the mitral valve 17. The three distinct sealing regionsare: an anterior region 25 a, a posterior region 25 b, and twocommissural regions 25 c. The anterior region 25 a extends generallylinearly between the left and right trigones 134 a and 134 b. Theposterior region 25 b comprises the middle scallop 24 b and posteriorportions of the lateral scallop 24 a and medial scallop 24 c. Thecommissural regions 25 c extend between the anterior region 25 a and theposterior region 25 b. The commissural regions 25 c generally encompassthe commissures 30 a and 30 b, and anterior portions of the lateralscallop 24 a and medial scallop 24 c. These three sealing regions 25 a,25 b, and 25 c will be referenced again in regard to FIGS. 28-33.

Referring to FIG. 26, a schematic diagram of a cross-section of a nativemitral 17 valve indicates the location of the mitral valve annulus 28.Three geometric variables (S, W, and H) that can be used to quantify arelative geometric orientation of sealing surfaces on the prostheticvalve in relation to the annulus 28 of the native mitral valve 17 arealso indicated. As used herein, the term “sealing surfaces” is definedas surface areas on the prosthetic valve that are intended to makesealing contact with structures of the native mitral valve 17(especially the leaflets of the native mitral valve 17). Hence, thesealing surfaces are the areas on the prosthetic valve that are used tofacilitate the leaflet to valve body seal.

The geometric variable S quantifies the radial distance from the annulus28 to the adjacent prosthetic valve framework surface. A negativeS-value indicates that the annulus 28 and the adjacent prosthetic valvesurface are spaced apart from each other. For example, an S-value ofnegative 2 mm indicates that there is a 2 mm space between the annulus28 and the adjacent prosthetic valve surface. When S equals zero, itindicates that the annulus 28 and the adjacent prosthetic valve surfaceare in contact with each other in a line-to-line fit relationship. WhenS is a positive number, it indicates that the annulus 28 and theadjacent prosthetic valve surface are in an interference fitrelationship. In other words, when S is a positive number somecompressive force is being applied to the annulus 28 by the adjacentprosthetic valve surface.

The geometric variable H quantifies the distance from the superior limit(upper edge) to the inferior limit (lower edge) of the sealing surfaceon the prosthetic valve. H-values are measured downward (in reference tothe illustration). For example, an H-value of 10 mm indicates that, fora particular sealing region, the sealing surface on the prosthetic valveends 10 mm below the superior limit of the sealing surface. In anotherexample, when the superior limit is at the annulus 28, an H-value of 7mm indicates that the inferior limit of the sealing surface is 7 mmbelow the annulus 28. In general, the superior limit of the sealingsurface on the prosthetic valve is either at, slightly above, orslightly below the annulus 28 (e.g., about 2 mm above or about 2 mmbelow the annulus 28 in some embodiments).

The geometric variable W quantifies the radial distance from thesuperior limit of the sealing surface to the inferior limit of thesealing surface on the prosthetic valve. A negative W-value indicatesthat the inferior limit of the sealing surface is positioned radiallyinward in comparison to the superior limit of the sealing surface (e.g.,at least a portion of the sealing surface is flared or bowed inward atthe distal end). A positive W-value indicates that the inferior limit ofthe sealing surface is positioned radially outward in comparison tosuperior limit of the sealing surface (e.g., at least a portion of thesealing surface is flared or bowed outward at the distal end). A W-valueof zero indicates that the inferior limit of the sealing surface ispositioned at the same radial position as the superior limit of thesealing surface.

Referring to FIG. 27, an anterior side view of a valve assembly 300includes an anterior sealing surface 360 a in accordance with someembodiments. In the depicted embodiment, the anterior sealing surface360 a spans the lower portion of the anterior side of valve assembly300. The anterior sealing surface 360 a comprises the surface area onthe anterior side of the prosthetic valve assembly 300 that is intendedto make sealing contact with structures of the native mitral valve. Theanterior sealing surface 360 a consists of structural support from thevalve frame 301 as well as a tissue surface 361 a. The anterior tissuesurface 361 a provides sealing interface height (H) but its flexiblenature reduces the amount of LVOT obstruction, as will be describedlater. For example, at least a portion of the anterior sealing surface360 a is intended to make sealing contact with the anterior leaflet ofthe native mitral valve.

Referring to FIG. 28, a posterior side view of a valve assembly 300includes a posterior sealing surface 360 b in accordance with someembodiments. In the depicted embodiment, the posterior sealing surface360 b spans the lower portion of the posterior side of valve assembly300. The posterior sealing surface 360 b comprises the surface area onthe posterior side of the prosthetic valve assembly 300 that is intendedto make sealing contact with structures of the native mitral valve. Forexample, at least a portion of the posterior sealing surface 360 b isintended to make sealing contact with the posterior leaflet of thenative mitral valve.

Referring to FIG. 29, a commissural (lateral) side view of a valveassembly 300 includes a commissural sealing surface 360 c in accordancewith some embodiments. This view is slightly biased to the anterior sideof the valve assembly 300. In the depicted embodiment, the commissuralsealing surface 360 c spans the lower portion of the commissural side ofvalve assembly 300. The commissural sealing surface 360 c comprises thesurface area on the lateral side of the prosthetic valve assembly 300that is intended to make sealing contact with structures of the nativemitral valve. For example, at least a portion of the commissural sealingsurface 360 c is intended to make sealing contact with the medialscallop or the lateral scallop of the posterior leaflet of the nativemitral valve, and with the leaflet tissue in the commissural regions ofthe native mitral valve.

Referring to FIG. 30, the geometric relationship between a native mitralvalve annulus and an anterior sealing surface of a prosthetic mitralvalve in accordance with some embodiments can be represented by the S,H, and W values as described above in reference to FIG. 26. For example,in some embodiments the S-value of the anterior sealing surface of theprosthetic mitral valve is in a range from about zero millimeters toabout positive 2 millimeters. In other words, the S-value of theanterior sealing surface in relation to the native mitral valve annulusis in a range from about line-to-line contact to about 2 millimetersinterference. It should be understood that in this context aninterference fit does not necessarily mean that the native valve annulusis stretched or deformed as a result of the interference. More likely,rather, the prosthetic valve assembly will be inhibited by the annulusfrom enlarging to its unconstrained fully expanded size. While in thedepicted embodiment the S-value is in a range of about zero millimetersto about positive 2 millimeters, in some embodiments the S-value is in arange of about negative 2 millimeters to about positive 1 millimeter, orabout negative 1 millimeter to about positive 3 millimeters, or aboutzero millimeters to about positive 4 millimeters. In some embodiments,the S-value can be more negative than about negative 2 millimeters ormore positive than about positive 4 millimeters.

In some embodiments the H-value of the anterior sealing surface of theprosthetic mitral valve is about 14 millimeters. In other words, in someembodiments the distance from the superior edge of the anterior sealingsurface to the inferior edge of the anterior sealing surface is about 14millimeters. More specifically, the H-value of the anterior sealingsurface can be divided into two portions: (1) a superior portion,H_(LVOT) and (2) an inferior portion, H_(TISSUE). The H_(LVOT)-valuegenerally corresponds to the distance from the superior edge of theanterior sealing surface to the inferior end of the valve frame 301 atvarious places along the anterior sealing surface 360 a (refer to FIG.27). The H_(TISSUE)-value corresponds to the distance from the inferiorend of the valve frame 301 at various places along the anterior sealingsurface 360 a to the inferior end of the anterior tissue surface 361 aat those places. While in the depicted embodiment, the H_(LVOT)-valueand the H_(TISSUE)-value are equal to each other, in some embodimentsthe ratio between the H_(LVOT)-value and the H_(TISSUE)-value is about3:1, about 2:1, about 1.5:1, about 1:1.5, about 1:2, or about 3:1.

While in the depicted embodiment the total H-value is about 14millimeters, in some embodiments the H-value is in a range of about 8millimeters to about 10 millimeters, or about 10 millimeters to about 12millimeters, or about 12 millimeters to about 14 millimeters, or about14 millimeters to about 16 millimeters, or about 13 millimeters to about15 millimeters. In some embodiments, the H-value can be less than about8 millimeters or more than about 16 millimeters.

In some embodiments the W-value of the anterior sealing surface of theprosthetic mitral valve is about negative 2 millimeters. In other words,in some embodiments the radial distance from the superior edge of theanterior sealing surface to the inferior edge of the anterior sealingsurface on the prosthetic valve is about negative 2 millimeters. AW-value of negative 2 millimeters indicates that the lower edge of theanterior sealing surface is positioned radially inward in comparison tothe superior edge of the anterior sealing surface by about 2millimeters. This also indicates that the sub-annular anterior valveassembly is flared or bowed inward, such as indicated by valve bodyprofile line 362 a. While in the depicted embodiment the W-value isabout negative 2 millimeters, in some embodiments the W-value is in arange of about negative 6 millimeters to about negative 4 millimeters,or about negative 4 millimeters to about negative 2 millimeters, orabout negative 2 millimeters to about zero millimeters, or about zeromillimeters to about positive 2 millimeters, or about negative 3millimeters to about negative 1 millimeter. In some embodiments, theW-value can be more negative than about negative 6 millimeters or morepositive than about positive 2 millimeters.

Referring to FIG. 31, the geometric relationship between a native mitralvalve annulus and a commissural sealing surface of a prosthetic mitralvalve in accordance with some embodiments can be represented by the S,H, and W values as described above in reference to FIG. 26. For example,in some embodiments the S-value of the commissural sealing surface ofthe prosthetic mitral valve is in a range from about zero millimeters toabout positive 2 millimeters. In other words, the S-value of thecommissural sealing surface in relation to the native mitral valveannulus is in a range from about line-to-line contact to about 2millimeters interference. It should be understood that in this contextan interference fit does not necessarily mean that the native valveannulus is stretched or deformed as a result of the interference. Morelikely, rather, the prosthetic valve assembly will be inhibited by theannulus from enlarging to its fully expanded size. While in the depictedembodiment the S-value is in a range of about zero millimeters to aboutpositive 2 millimeters, in some embodiments the S-value is in a range ofabout negative 2 millimeters to about positive 1 millimeter, or aboutnegative 1 millimeter to about positive 3 millimeters, or about zeromillimeters to about positive 4 millimeters. In some embodiments, theS-value can be more negative than about negative 2 millimeters or morepositive than about positive 4 millimeters.

In some embodiments, the H-value of the commissural sealing surface ofthe prosthetic mitral valve is in a range of about 8 millimeters toabout 14 millimeters. In other words, in some embodiments the distancefrom the native valve annulus to the lower (inferior) edge of thecommissural sealing surface is in a range of about 8 millimeters toabout 14 millimeters. This range, from about 8 millimeters to about 14millimeters, is at least partly a result of the shape of a commissuralcorner 364 (refer to FIG. 29) that comprises part of the commissuralsealing surface. Accordingly, the lower edge of the commissural sealingsurface varies across the lateral width of the commissural sealingsurface just by the nature of the shape of the commissural sealingsurface. While in the depicted embodiment the H-value is in a range ofabout 8 millimeters to about 14 millimeters, in some embodiments theH-value is in a range of about 4 millimeters to about 10 millimeters, orabout 6 millimeters to about 12 millimeters, or about 8 millimeters toabout 14 millimeters, or about 10 millimeters to about 16 millimeters,or about 7 millimeters to about 15 millimeters. In some embodiments, theH-value can be less than about 4 millimeters or more than about 15millimeters.

In some embodiments the W-value of the commissural sealing surface ofthe prosthetic mitral valve is about negative 2 millimeters. In otherwords, in some embodiments the radial distance from the superior (upper)edge of the commissural sealing surface to the inferior (lower) edge ofthe commissural sealing surface on the prosthetic valve is aboutnegative 2 millimeters. A W-value of negative 2 millimeters indicatesthat the lower edge of the commissural sealing surface is positionedradially inward in comparison to the upper edge of the commissuralsealing surface by about 2 millimeters. This also indicates that thesub-annular commissural valve assembly is flared or bowed inward, suchas indicated by valve body profile line 362 b. While in the depictedembodiment the W-value is about negative 2 millimeters, in someembodiments the W-value is in a range of about negative 6 millimeters toabout negative 4 millimeters, or about negative 4 millimeters to aboutnegative 2 millimeters, or about negative 2 millimeters to about zeromillimeters, or about zero millimeters to about positive 2 millimeters,or about negative 3 millimeters to about negative 1 millimeter. In someembodiments, the W-value can be more negative than about negative 6millimeters or more positive than about positive 2 millimeters.

Referring to FIG. 32, the geometric relationship between a native mitralvalve annulus and a posterior sealing surface of a prosthetic mitralvalve in accordance with some embodiments can be represented by the S,H, and W values as described above in reference to FIG. 26. For example,in some embodiments the S-value of the posterior sealing surface of theprosthetic mitral valve is in a range from about zero millimeters toabout positive 2 millimeters. In other words, the S-value of theposterior sealing surface in relation to the native mitral valve annulusis in a range from about line-to-line contact to about 2 millimetersinterference. It should be understood that in this context aninterference fit does not necessarily mean that the native valve annulusis stretched or deformed as a result of the interference. More likely,rather, the prosthetic valve assembly will be inhibited by the annulusfrom enlarging to its fully expanded size. While in the depictedembodiment the S-value is in a range of about zero millimeters to aboutpositive 2 millimeters, in some embodiments the S-value is in a range ofabout negative 2 millimeters to about positive 1 millimeter, or aboutnegative 1 millimeter to about positive 3 millimeters, or about zeromillimeters to about positive 4 millimeters. In some embodiments, theS-value can be more negative than about negative 2 millimeters or morepositive than about positive 4 millimeters.

In some embodiments, the H-value of the posterior sealing surface of theprosthetic mitral valve is about 8 millimeters. In other words, in someembodiments the distance from the native valve annulus to the lower(inferior) edge of the posterior sealing surface is about 8 millimeters.While in the depicted embodiment the H-value is about 8 millimeters, insome embodiments the H-value is in a range of about 4 millimeters toabout 6 millimeters, or about 6 millimeters to about 8 millimeters, orabout 8 millimeters to about 10 millimeters, or about 10 millimeters toabout 12 millimeters, or about 7 millimeters to about 9 millimeters. Insome embodiments, the H-value can be less than about 4 millimeters ormore than about 12 millimeters.

In some embodiments, the W-value of the posterior sealing surface of theprosthetic mitral valve is about positive 2 millimeters. In other words,in some embodiments the radial distance from the upper (superior) edgeof the posterior sealing surface to the lower (inferior) edge of theposterior sealing surface on the prosthetic valve is about positive 2millimeters. A W-value of positive 2 millimeters indicates that thelower edge of the posterior sealing surface is positioned radiallyoutward in comparison to the upper edge of the posterior sealing surfaceby about 2 millimeters. This also indicates that the sub-annularposterior valve assembly is flared or bowed outward, such as indicatedby valve body profile line 362 c. While in the depicted embodiment theW-value is about positive 2 millimeters, in some embodiments the W-valueis in a range of about negative 4 millimeters to about negative 2millimeters, or about negative 2 millimeters to about zero millimeters,or about zero millimeters to about positive 2 millimeters, or aboutpositive 2 millimeters to about positive 4 millimeters, or aboutpositive 1 millimeter to about positive 3 millimeters. In someembodiments, the W-value can be more negative than about negative 2millimeters or more positive than about positive 3 millimeters.

Referring to FIG. 33, during systole the aortic valve 510 receives bloodflowing out from the left ventricle 18. The blood flows to the aorticvalve 510 via a left ventricular outflow tract (LVOT) 512. In somecircumstances, a prosthetic mitral valve 600 (shown without an anchorassembly for simplicity) implanted in the native mitral valve 17 mayobstruct the LVOT 512, as represented by an obstruction 514, resultingin reduced ejection of blood from the left ventricle 18. As describedherein, the prosthetic mitral valves provided by this disclosure may beconfigured to reduce or eliminate LVOT obstructions 514.

Referring to FIGS. 34 and 35, a first fluoroscopic image 700 and asecond fluoroscopic image 730 were obtained after fluoroscopic dye wasinjected into the left ventricle to enhance visualization of blood flowand blood flow obstructions. The images show blood flowing from the leftventricle to the aorta through the left ventricular outflow track(LVOT).

The first fluoroscopic image 700 illustrates an area of reduced bloodflow 710 caused by an LVOT obstruction from a prosthetic mitral valve720. The second fluoroscopic image 730 illustrates improved blood flow740 through the LVOT. The improved blood flow 740 can be a result ofless obstruction attributable to the prosthetic mitral valve 750. Forexample, in some embodiments the prosthetic mitral valve 750 can bepositioned or designed so that less structure of the valve 750 is belowthe native mitral valve annulus, resulting in less structure of thevalve 750 within the LVOT. Additionally, the prosthetic mitral valve 750can be positioned or designed so that less structure of the valve 750 iswithin the LVOT such as by tapering, bowing, or shaping the structureaway from the LVOT.

Referring again to FIG. 33, the portion of the prosthetic mitral valve600 that faces the aortic valve 510 is the anterior sealing surface 625a. Therefore, the geometric orientation of the anterior sealing surface625 a in relation to the LVOT 512 is a factor relating to whether or notthe prosthetic mitral valve 600 will cause obstructions 514.

Referring also to FIG. 36, the geometric relationships between the LVOT512, the native mitral valve annulus 28, and the anterior sealingsurface variables (S-value, H-value, and W-value, as described inreference to FIGS. 25, 26, and 30) can be used to quantify LVOTobstructions 514. The angle between the LVOT 512 and the native mitralvalve annulus 28 is identified as θ. The R-value is a variable thataccounts for prosthetic valve positioning variations from theanticipated/ideal location of the prosthetic valve relative to thenative valve annulus.

Using geometry, the LVOT obstruction 514 distance (identified as “O” inthe equation below) can be calculated using the following equation:

$O = {{R\; \sin \; \theta} + {\sqrt{W^{2} + H_{LVOT}^{2}}\sin \left\{ {\theta - {\tan^{- 1}\left( \frac{W}{H} \right)}} \right\}} - {S\; \cos \; \theta}}$

where:

-   -   O is the calculated distance of an LVOT obstruction;    -   R is the distance from the native valve annulus to the top of        the anterior sealing surface;    -   θ is the angle between the mitral valve annulus and the LVOT;    -   W is the radial distance from the upper edge of the sealing        surface to the lower edge of the sealing surface on the        prosthetic valve;    -   H_(LVOT) is the distance from the superior edge of the sealing        surface to the lower structural (frame) edge of the sealing        surface on the prosthetic valve: and    -   S is the radial distance from the mitral valve annulus to the        adjacent prosthetic valve surface.

The following examples are provided to illustrate Equation #1 above.

H_(LVOT) Example R (mm) S (mm) (mm) W (mm) θ° O (mm) 1 0 2 8 −2 164 2.22 0 0 8 −2 119 6.0 3 0 2 8 −4 119 6.0 4 0 2 5 −4 119 3.4 5 0 0 14 −2 1641.9

By comparing Examples #1 and #5, with Examples #2, #3, and #4 it can beascertained that O (the LVOT obstruction) tends to be less when θ isgreater. By comparing Example #3 and Example #4, it is seen that agreater H_(LVOT) tends to result in a higher O. By comparing Example #2and Example #3, it can be determined that the effect of a greaterS-value can be offset by a more negative W-value. In summary, one ofordinary skill in the art can use these teachings to select an R-value,S-value, H_(LVOT)-value, and W-value for a given θ (based on patientanatomy) in effort to attain an acceptable O (the LVOT obstruction).

Referring to FIGS. 37 and 38, an anchor assembly 200 can be engaged witha native mitral valve 17 such that the feet 220 a, 220 b, 220 c, and 220d are seated in the sub-annular gutter 19 of the native mitral valve 17,while the leaflets 20 and 22 and chordae tendineae 40 are substantiallyunhindered by the anchor assembly 200. As described above, the anchorassembly 200 is designed to be implanted within a native mitral valve17, without substantially interfering with the native valve 17, so thatthe native valve 17 can continue to function as it did prior to theplacement of the anchor assembly 200. To accomplish that, the leaflets20 and 22 and chordae tendineae 40, especially the chordae tendineae 40that are attached to the anterior leaflet 20, need to be substantiallyunhindered by the anchor assembly 200.

In some implementations, the positioning of the hub 210 relative to theanatomical features of the mitral valve 17 is relevant to facilitatingsubstantially unhindered leaflets 20 and 22 and chordae tendineae 40.For example, a depth 810 of the hub 210 in the left ventricle 18 is onerelevant consideration. In order to substantially prevent hindrances tothe leaflets 20 and 22 and chordae tendineae 40, the depth 810 should beat least slightly below the coaptation depth of the mitral valve 17. Thecoaptation depth is the greatest vertical distance from the annulus ofthe mitral valve 17 to an area of coaptation between the native leaflets20 and 22. Hence, positioning the hub 210 below the coaptation depthwill facilitate substantially unhindered leaflets 20 and 22 and chordaetendineae 40. In some implementations, the depth 810 is in a range ofabout 14 mm to about 20 mm, or about 10 mm to about 16 mm, or about 12mm to about 18 mm, or about 16 mm to about 22 mm. In someimplementations, the depth 810 is less than about 10 mm or greater thanabout 22 mm.

The positioning of the hub 210 relative to the line of coaptationbetween the leaflets 20 and 22 (e.g., the line of coaptation 32 shown inFIG. 8) is also relevant to facilitating substantially unhinderedleaflets 20 and 22 and chordae tendineae 40. For example, in someimplementations positioning the hub 210 generally in vertical alignmentwith the line of coaptation will serve to substantially preventhindrances to the leaflets 20 and 22 and the chordae tendineae 40.

In some implementations, the angular positioning of the left anteriorsub-annular support arm 230 a, the left posterior sub-annular supportarm 230 b, the right posterior sub-annular support arm 230 c, and theright anterior sub-annular support arm 230 d in relation to the nativemitral valve 17 is relevant to facilitating substantially unhinderedleaflets 20 and 22 and chordae tendineae 40. In some implementations,the sub-annular support arms 230 a, 230 b, 230 c, and 230 d are arrangedsymmetrically in relation to a left ventricular long axis (LAX) 840.That is, the LAX 840 bisects an anterior support arm angle 830 and aposterior support arm angle 820.

To minimize disturbances to the anterior leaflet 20 and chordaetendineae 40, the anterior support arms 220 a and 220 d are positionedessentially between the chordae tendineae 40. In some embodiments, theanterior support arm angle 830 is in a range of about 100° to about135°, or about 80° to about 120°, or about 120° to about 160°. Tominimize disturbances to the posterior leaflet 22 and chordae tendineae40, in some implementations the posterior support arms 220 b and 220 bmay extend essentially amongst the chordae tendineae 40. In someembodiments, the posterior support arm angle 820 is in a range of about50° to about 120°, or about 40° to about 80°, or about 60° to about100°, or about 80° to about 120°, or about 100° to about 140°.

A number of embodiments of the invention have been described.Nevertheless, it will be understood that various modifications may bemade without departing from the scope of the invention. Accordingly,other embodiments are within the scope of the following claims.

What is claimed is:
 1. A prosthetic mitral valve system comprising: avalve assembly comprising: a frame member defining an outer profile andan interior frame member space; and an occluder disposed within theinterior frame member space, the occluder having an open configurationand a closed configuration, wherein the frame member comprises aproximal end frame portion and a distal end frame portion, wherein anouter periphery of the distal end frame portion comprises a generallyflat region and a generally round region, and wherein at least someportions of the generally flat region extend distally toward theinterior frame member space.
 2. The prosthetic mitral valve of claim 1,further comprising an anchor assembly defining an interior anchorassembly space, wherein the valve assembly is selectively mate-able withthe interior anchor assembly space.
 3. The prosthetic mitral valve ofclaim 2, wherein the anchor assembly comprises an expandable anchorframe including a hub and a sub-annular support arm extending from thehub, wherein the sub-annular support arm extends to an anchor foothaving a surface configured for engagement with a sub-annular gutter ofa native mitral valve.
 4. The prosthetic mitral valve of claim 3,wherein a distance measured parallel to a longitudinal axis of the valveassembly from a distal-most end of the anchor assembly to the surface isat least 14 millimeters.
 5. The prosthetic mitral valve of claim 1,wherein the distal end frame portion comprises a generally D-shapedouter periphery, and wherein the proximal end frame portion comprises acircular valve orifice located radially inward from the generallyD-shaped outer peripheral region and carrying valve leaflets that definea circular perimeter at the circular valve orifice.
 6. A method of usinga prosthetic mitral valve system, comprising: advancing a valve assemblyof the prosthetic mitral valve system toward an annulus of a nativemitral valve, the valve assembly comprising: a frame member defining anouter profile and an interior frame member space; and an occluderdisposed within the interior frame member space, the occluder having anopen configuration and a closed configuration, wherein the frame membercomprises a proximal end frame portion and a distal end frame portion,wherein an outer periphery of the distal end frame portion comprises agenerally flat region and a generally round region, and wherein at leastsome portions of the generally flat region extend toward the interiorframe member space; and anchoring the valve assembly at the nativemitral valve such that the generally flat region is adjacent to ananterior native leaflet of the native mitral valve.
 7. The method ofclaim 6, further comprising, prior to implanting the valve assembly,engaging an anchor assembly of the prosthetic mitral valve system withtissue proximate to an annulus of the native mitral valve, the anchorassembly defining an interior anchor assembly space, and wherein saidanchoring the valve assembly comprises interlocking the valve assemblywithin the interior anchor assembly space.
 8. The method of claim 7,wherein the anchor assembly comprises an expandable anchor frameincluding a hub and a sub-annular support arm extending from the hub,wherein the sub-annular support arm extends to an anchor foot having asurface configured for engagement with a sub-annular gutter of thenative mitral valve.
 9. The method of claim 8, wherein a distancemeasured parallel to a longitudinal axis of the valve assembly from adistal-most end of the anchor assembly to the surface is at least 14millimeters.
 10. The method of claim 6, wherein the distal end frameportion comprises a generally D-shaped outer periphery, and wherein theproximal end frame portion comprises a circular valve orifice locatedradially inward from the generally D-shaped outer peripheral region andcarrying valve leaflets that define a circular perimeter at the circularvalve orifice.
 11. A prosthetic mitral valve system that is implantableat a native mitral valve, the prosthetic mitral valve system comprising:an anchor assembly defining an interior anchor assembly space and alongitudinal axis, the anchor assembly comprising an expandable anchorframe including a hub and a sub-annular support arm extending from thehub, wherein the sub-annular support arm extends to an anchor foothaving a surface configured for engagement with a sub-annular gutter ofthe native mitral valve; and a valve assembly comprising: an expandablevalve frame defining an outer profile and an interior frame memberspace; and an occluder disposed within the interior frame member space,the occluder having an open configuration and a closed configuration,wherein the valve assembly is releasably engageable with the anchorassembly within the interior anchor assembly space, and wherein adistance measured parallel to the longitudinal axis from a distal-mostend of the anchor assembly to the surface is at least 14 millimeters.12. The prosthetic mitral valve system of claim 11, wherein the valveassembly comprises a distal end frame portion having a generallyD-shaped outer periphery, and wherein the valve assembly comprises aproximal end frame portion having a circular valve orifice locatedradially inward from the generally D-shaped outer peripheral region andcarrying valve leaflets that define a circular perimeter at the circularvalve orifice.
 13. A method of using a prosthetic mitral valve system,the method comprising: advancing an anchor assembly of the prostheticmitral valve system toward an annulus of a native mitral valve, theanchor assembly defining an interior anchor assembly space andlongitudinal axis, the anchor assembly comprising an expandable anchorframe including a hub and one or more sub-annular support arms extendingfrom the hub, wherein each of the one or more sub-annular support armextends to an anchor foot configured to engage with a sub-annular gutterof the native mitral valve; and engaging the anchor assembly of theprosthetic mitral valve system with tissue proximate the native mitralvalve such that a surface of each anchor foot is engaged with thesub-annular gutter, and such that the hub is positioned distal of thedistal-most area of coaptation between anterior and post leaflets of thenative mitral valve.
 14. The method of claim 13, further comprisingdelivering a valve assembly of the prosthetic mitral valve system to theanchor assembly after engaging the anchor assembly with said tissueproximate the native mitral valve, a valve assembly comprising: anexpandable valve frame defining an outer profile and an interior framemember space, and an occluder disposed within the interior frame memberspace, the occluder having an open configuration and a closedconfiguration.
 15. The method of claim 14, wherein the valve assemblycomprises a distal end frame portion having a generally D-shaped outerperiphery, and wherein the valve assembly comprises a proximal end frameportion having a circular valve orifice located radially inward from thegenerally D-shaped outer peripheral region and carrying valve leafletsthat define a circular perimeter at the circular valve orifice.
 16. Themethod of claim 14, wherein a distance measured parallel to alongitudinal axis of the valve assembly from a distal-most end of theanchor assembly to the surface of at least one anchor foot is at least14 millimeters.
 17. A prosthetic mitral valve system comprising: ananchor assembly comprising an expandable anchor frame and a set ofsub-annular anchor feet configured to engage with a sub-annular gutterof a native mitral valve; and a valve assembly comprising: an expandablevalve frame defining an outer profile and an interior frame memberspace, a tissue layer disposed over at least a portion of the outerprofile, and an occluder mounted within the interior frame member space,wherein an outwardly facing periphery of the tissue layer along thevalve assembly is positioned to abut native leaflets of the mitral valvewhen the set of anchor feet of the anchor assembly is engaged with thesub-annular gutter.
 18. The prosthetic mitral valve system of claim 17,wherein the valve assembly comprises a distal end frame portion having agenerally D-shaped outer periphery, and wherein the valve assemblycomprises a proximal end frame portion having a circular valve orificelocated radially inward from the generally D-shaped outer peripheralregion and carrying valve leaflets that define a circular perimeter atthe circular valve orifice.
 19. A method of sealing between a prostheticmitral valve system and native leaflets of a mitral valve, the methodcomprising: anchoring an anchor assembly of the prosthetic mitral valvesystem with tissue proximate to an annulus of a native mitral valve, theanchor assembly defining an interior anchor assembly space andlongitudinal axis, the anchor assembly comprising an expandable anchorframe including a hub and one or more sub-annular support arms extendingfrom the hub, wherein each of the one or more sub-annular support armextends to an anchor foot that engages with a sub-annular gutter of thenative mitral valve; and delivering a valve assembly of the prostheticmitral valve system to engage with the anchor assembly, the valveassembly comprising: an expandable valve frame defining an outer profileand an interior frame member space; a tissue layer disposed over atleast a portion of the outer profile; and an occluder disposed withinthe interior frame member space, the occluder having an openconfiguration and a closed configuration, wherein the tissue layer ofthe valve assembly abuts with native leaflets of the mitral valve whileeach anchor foot of the anchor assembly is engaged with the sub-annulargutter.
 20. The method of claim 19, wherein the valve assembly comprisesa distal end frame portion having a generally D-shaped outer periphery,and wherein the valve assembly comprises a proximal end frame portionhaving a circular valve orifice located radially inward from thegenerally D-shaped outer peripheral region and carrying valve leafletsthat define a circular perimeter at the circular valve orifice.